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Rocky  Mountain 
Spotted  Fever 


The  Henry  E.  Sigerist  Series 
in  the  History  of  Medicine 

sponsored  by  The  American  Association  for  the  History 
of  Medicine  and  The  Johns  Hopkins  University  Tress 

The  Development  of  American  Physiology 
Scientific  Medicine  in  the  Nineteenth  Century 
by  W.  Bruce  Fye 

Save  the  Babies 

American  Tublic  Health  Reform  and  the 
Trevention  of  Infant  Mortality,  18^0-1919 
by  Richard  A.  Meckel 

Politics  and  Public  Health  in  Revolutionary 
Russia,  1890-1918 
by  John  F.  Hutchinson 

Rocky  Mountain  Spotted  Fever 
History  of  a  Twentieth-Century  Disease 
by  Victoria  A.  Harden 


^  LIBRARY 

^  JAN  1  7  1991 

National  Institutes  of  Health 

^  Rocky  Mountain 
Spotted  Fever 

History  of  a 

Twentieth-Century  Disease 


Victoria  A.  Harden 


The  Johns  Hopkins  University  Press 
Baltimore  and  London 


The  text  for  this  book  was  prepared  in  the  main  part  as 
an  intramural  project  of  the  National  Institute  of  Allergy 
and  Infectious  Diseases,  National  Institutes  of  Health. 

Foreword  ©  1990  The  Johns  Hopkins  University  Press 

Printed  in  the  United  States  of  America 

All  rights  reserved 

The  Johns  Hopkins  University  Press 

701  West  40th  Street 

Baltimore,  Maryland  21 211 

The  Johns  Hopkins  Press  Ltd.,  London 

The  paper  used  in  this  publication  meets  the  minimum  requirements  of  Ameri- 
can National  Standard  for  Information  Sciences— Permanence  of  Paper  for 
Printed  Library  Materials,  ansi  Z39. 48-1984. 

Library  of  Congress  Cataloging-in-Publication  Data 

Harden,  Victoria  Angela. 

Rocky  Mountain  spotted  fever:  history  of  a  twentieth-century 
disease  /  Victoria  A.  Harden. 

p.       cm.  —  (The  Henry  E.  Sigerist  series  in  the  history  of 

medicine) 
Includes  bibliographical  references. 
ISBN  0-8018-3905-X  (alk.  paper) 

1.  Rocky  Mountain  spotted  fever— History.  I.  Title.  II.  Series. 
RC182.R6H37  1990 

6i6.9'223— dc2o  89-48033 

CIP 


To  the  memory  of 
John  R.  Seal 

who  envisioned  this  history 

and  to 

William  L.  Jellison 

who  preserved  so  many  of  the  documents  on 
which  it  is  based 


Contents 


List  of  Illustrations  ix 
Foreword  xi 
Preface  xiii 

1  A  Twentieth-Century  Disease  of  Nature  i 

2  A  Blight  on  the  Bitterroot  9 

3  The  Beginning  of  Scientific  Investigations  23 

4  Dr.  Ricketts's  Discoveries  47 

5  Tick  Eradication  Efforts,  1911-1920  72 

6  A  Wholly  New^  Type  of  Microorganism  loi 

7  The  Spencer-Parker  Vaccine  119 

8  Spotted  Fever  outside  the  Rockies  147 

9  Dr.  Cox's  Versatile  Egg  175 

10  Spotted  Fever  Therapy, 

from  Sage  Tea  to  Tetracycline  197 

11  Spotted  Fever  after  Antibiotics  219 

12  Mysteries  Explained,  Mysteries  Remaining  240 

Abbreviations  261 
Notes  265 
Note  on  Sources  347 
Index  359 


Illustrations 


Rash  of  Rocky  Mountain  spotted  fever  4 

Known  distribution  of  Rocky  Mountain  spotted  fever, 
ca.  1900  13 

Louis  B.  Wilson  and  William  M.  Chow^ning  25 

Epidemiology  of  Rocky  Mountain  spotted  fever  in  the  Bitterroot 
Valley,  Montana,  1902  27 

Rocky  Mountain  wood  tick,  male  and  female  Dermacentor 
andersoni        3  o 

Charles  Wardell  Stiles  41 

Howard  Taylor  Ricketts        5 1 

Interior  of  Howard  Taylor  Ricketts's  tent  laboratory  52 
Ticks  waiting  on  vegetation  for  a  host  73 
Robert  A.  Cooley  78 

Flagging  for  ticks  in  the  Bitterroot  Valley  80 

Buildings  in  Victor,  Montana,  used  as  a  laboratory  by  U.S.  PubHc 
Health  Service,  1911-16  83 

Thomas  B.  McClintic  87 

Lunsford  D.  Fricks  88 

Dipping  vat  in  the  Bitterroot  Valley  92 

S.  Burt  Wolbach  104 

S.  Burt  Wolbach's  drawing  of  the  spotted  fever  organism  in  the 
tissues  of  infected  animals  108 

Schoolhouse  laboratory  121 

Roscoe  R.  Spencer  and  Ralph  R.  Parker  123 

William  Edwin  Gettinger,  George  Henry  Cowan,  and 
Albert  LeRoy  Kerlee  131 

ix 


Illustrations 


Tubes  in  the  tick-rearing  process  134 


Laboratory  technician  decanting  Spencer-Parker  vaccine  into  bottles 
for  shipment,  193 1  134 

Rocky  Mountain  Laboratory,  1928  141 

Vaccinating  against  spotted  fever,  193 1  145 

Rolla  E.  Dyer  149 

Dermacentor  variabilis,  vector  of  Rocky  Mountain  spotted  fever  in 
the  eastern  United  States  151 

Distribution  of  Rocky  Mountain  spotted  fever  in  the  United  States, 
1933  160 

Distribution  of  Rocky  Mountain  spotted  fever  in  the  United  States, 
1941  166 

Letters  and  telegrams  requesting  bottles  of  the 
Spencer-Parker  vaccine  171 

Ida  A.  Bengtson  176 

Herald  R.  Cox  179 

Technician  harvesting  yolk  sacs  from  eggs  infected  with  rickettsial 
organisms  182 

Rocky  Mountain  Laboratory  during  World  War  II  187 
Norman  H.  Topping  207 

Broad-spectrum  antibiotics  that  cured  Rocky  Mountain  spotted 
fever  214 

Deaths  and  ratios  of  cases  to  fatalities  of  Rocky  Mountain  spotted 
fever  in  the  United  States,  1940-70  220 

Reported  cases  of  Rocky  Mountain  spotted  fever  per  100,000 
population,  by  year,  in  the  United  States,  1955-83  235 

Willy  Burgdorfer  252 


Foreword 


One  of  the  factors  that  attracted  me  to  Rocky  Mountain  spotted 
fever  was  the  rich  historic  lore  of  the  subject.  Years  of  collecting  and 
studying  the  literature  of  the  field  confirmed  my  opinion  that  the  stories 
expressed  the  emergence  of  science  from  the  Western  frontier.  In  this 
book,  Victoria  Harden  conveys  the  history  v^ith  the  vividness  of  the 
traditional  storyteller  and  the  care  of  the  professional  historian.  What 
develops  is  the  picture  of  the  maturation  of  biomedical  science  in  the 
United  States.  Scientists  in  the  discipHnes  of  entomology,  microbiology, 
pathology,  medicine,  and  immunology  have  elucidated  a  novel  infec- 
tious agent  that  normally  resides  in  ticks.  They  began  v^ith  a  prevalent 
public  opinion  that  this  dreaded  plague  v^as  caused  by  drinking  w^ater 
from  melted  snov^  and  over  the  years  reached  a  more  accurate  state 
of  knowledge.  Because  of  the  dramatic  severity  of  the  clinical  illness, 
work  on  these  difficult  organisms  has  continued.  Rickettsiology  has 
now  overcome  many  of  the  technical  obstacles  that  for  so  long  inhibited 
progress.  By  employing  molecular  methods,  the  field  has  accelerated 
its  pace  and  is  now  in  the  mainstream  of  microbiology.  Genes  have 
been  cloned  for  important  rickettsial  components  and  specific  func- 
tions. The  power  of  science  to  make  significant  advances  in  rickett- 
siology has  never  been  greater. 

Yet  the  number  of  institutions  with  research  laboratories  that  are 
engaged  in  the  investigation  of  Rickettsia  rickettsii  and  its  relatives  are 
remarkably  few.  The  medical  importance  of  rickettsiae  alone  justifies 
considerably  more  effort.  Rocky  Mountain  spotted  fever  is  still  a  life- 
threatening  disease  for  healthy  persons  who  are  engaged  in  outdoor 
activities.  There  are  major  pitfalls  and  deficiencies  in  both  the  clinical 
and  laboratory  diagnoses  of  Rocky  Mountain  spotted  fever.  The  eti- 
ologic  agent  is  firmly  entrenched  in  nature  and  cannot  yet  be  eradicated. 
Related  rickettsiae  frequently  cause  undiagnosed  infections  in  southern 
Europe,  Africa,  and  Asia.  No  effective  vaccines  are  available.  Medical 
treatment  given  late  in  the  course  of  illness  because  of  delayed  diagnosis 
often  fails  to  save  the  patient's  life. 

In  addition  to  the  practical  problems,  there  are  many  interesting 
scientific  questions  about  rickettsiae  that  could  lead  to  better  under- 
standing of  intracellular  parasitism,  pathobiology  and  immunobiology 


XI 


xii 


Foreword 


of  intracellular  bacteria,  and  endothelial  pathophysiology.  Numerous 
basic  questions  remain  unanswered:  How  are  rickettsiae  maintained 
in  nature?  Is  rickettsial  infection  pathogenic  for  the  tick?  What  has 
prevented  pathogenic  R.  rickettsii  from  occupying  a  greater  proportion 
of  the  ecologic  niche  in  ticks  (less  than  o.i  percent  of  the  members  of 
the  major  vector  species  of  ticks  contain  disease-causing  R.  rickettsii)} 
How  do  the  more  prevalent  nonpathogenic  rickettsiae  interfere  with 
establishment  of  their  pathogenic  relatives?  Why  does  the  incidence 
and  geographic  distribution  of  disease  appear  to  change  during  a  period 
of  time?  What  components  of  the  immune  system  must  be  stimulated 
in  order  for  it  to  resist  infection  or  reinfection?  How  does  the  immune 
system  rid  the  human  host  of  an  established  infection?  What  is  the 
composition  of  rickettsiae  (e.g.,  what  is  the  composition  of  the  outer 
layer,  putatively  a  slime  layer?)?  How  do  the  rickettsial  structural 
components  mediate  the  various  functions  of  the  organism?  How  is 
virulence  reactivated  from  its  dormant  state  in  ticks?  How  do  host 
factors  such  as  older  age,  male  sex,  the  genetic  condition  of  glucose- 
6-phosphate  dehydrogenase  deficiency,  and  possibly  hemolysis  lead  to 
increased  severity  of  illness?  How  do  the  rickettsiae  cause  human  cell 
and  tissue  damage  and  disease  syndromes?  Do  so-called  nonpathogenic 
rickettsiae  such  as  R.  parkeri  and  R.  rhipicephali  infect  humans,  causing 
unrecognized  syndromes? 

The  number  of  fruitful  lines  of  inquiry  rapidly  overwhelms  the  corps 
of  rickettsiologists,  whose  ranks  are  already  thin.  The  specialized  cadre 
of  scientists  who  know  and  understand  rickettsiae  must  be  expanded 
by  educating  more  young  scientists,  and  more  funding  is  required  for 
significant  scientific  progress.  Rickettsiology  has  for  years  been  viewed 
as  archaic  even  as  it  has  quietly  opened  new  avenues  of  knowledge. 
Rickettsiologists  have  delved  into  topics  such  as  the  pathogenic  roles 
of  phospholipase  and  protease  or  the  role  of  interferon-gamma  in 
immunity  to  intracellular  pathogens.  They  have  solved  such  riddles  as 
the  cause  of  Legionnaires'  disease,  Lyme  disease,  and  Potomac  horse 
fever.  During  the  next  decade,  rickettsiologists  must  continue  to  do 
basic  laboratory  investigation,  teach  others  the  science  and  historic 
lore,  reach  out  to  collaborate  with  colleagues  abroad  on  the  prevalent 
infections  in  Asia,  Africa,  and  Europe.  It  is  hoped  that  in  the  process, 
important  new  scientific  advances  will  answer  questions  remaining 
from  the  early  days  of  studies  in  the  Bitterroot  Valley  of  western 
Montana.  It  is  even  reasonable  to  expect  better  approaches  to  pre- 
vention, diagnosis,  and  treatment.  The  pace  of  progress  may  be  ex- 
pected to  reflect  the  support  provided  by  public  and  private  agencies. 

David  H.  Walker,  M.D. 


Preface 


In  1984  I  was  invited  to  write  a  history  of  Rocky  Mountain  spotted 
fever  for  the  National  Institute  of  Allergy  and  Infectious  Diseases 
(NIAID),  the  component  of  the  National  Institutes  of  Health  (NIH) 
that  traces  its  roots  to  1 887,  when  federally  sponsored  medical  research 
began.  Since  1902,  NIAID  and  its  antecedent  laboratories  in  the  U.S. 
Public  Health  Service  have  supported  research  on  Rocky  Mountain 
spotted  fever.  The  late  John  R.  Seal,  in  1984  deputy  director  and 
formerly  director  of  intramural  research,  was  the  project's  initial  spon- 
sor within  the  institute.  He  believed  that  a  history  of  this  disease  would 
contribute  to  the  understanding  of  twentieth-century  medicine  and 
medical  research.  The  project  gained  the  support  of  NIAID  director 
Richard  M.  Krause  and  of  his  successor,  Anthony  S.  Fauci,  and  was 
placed  within  the  NIH  intramural  research  program.  I  began  the  work 
under  Kenneth  W.  Sell,  intramural  director,  who  framed  the  assignment 
in  broad  terms  and  provided  support  services  for  the  research.  His 
successor,  John  I.  Gallin,  continued  these  policies  and  graciously  ex- 
tended my  deadline  so  that  I  might  participate  in  preparations  for  the 
NIH  centennial  observance. 

Although  the  U.S.  Public  Health  Service  was  not  the  only  agency 
that  contributed  to  the  diagnosis,  prevention,  and  cure  of  Rocky  Moun- 
tain spotted  fever,  it  has  played  a  key  role  throughout  this  century. 
Because  spotted  fever  occurs  only  in  the  western  hemisphere  — but  not 
exclusively  in  the  Rocky  Mountain  region,  as  its  name  implies— it  held 
particular  interest  for  investigators  in  the  United  States  from  the  time 
it  was  first  differentiated  from  other  fevers.  During  the  early  decades 
of  the  twentieth  century,  much  of  the  work  on  spotted  fever  was 
conducted  at  laboratories  in  the  Bitterroot  Valley  of  western  Montana, 
where  the  disease  was  particularly  virulent.  A  laboratory  building 
initially  constructed  in  1928  by  the  state  of  Montana  subsequently 
became  the  Rocky  Mountain  Laboratory  (RML)  of  NIAID.  Fortu- 
nately for  the  historian,  many  of  the  investigators  at  the  RML  kept 
meticulous  records  and  saved  their  correspondence.  In  conjunction 
with  documents  at  other  institutions  and  with  the  published  scientific 
Uterature,  these  records  provided  a  rich  archival  source  for  the  prep- 
aration of  this  history.  During  the  course  of  the  project,  many  state 


xiii 


xiv 


Preface 


and  federal  records  at  the  RML  were  transferred  to  institutions  where 
they  will  be  preserved  and  made  available  to  other  scholars.  The  dis- 
position of  these  records  is  discussed  in  the  Note  on  Sources. 

During  the  years  of  research  for  and  writing  of  this  book,  I  have 
incurred  debts  to  many  people,  especially  in  Montana  and  at  the  NIH 
in  Bethesda,  Maryland.  These  included  scientists,  administrators,  lab- 
oratory support  staff,  archivists,  librarians,  other  historians,  and  lay 
persons  whose  lives  have  been  touched  by  Rocky  Mountain  spotted 
fever.  Many  of  these  people  are  acknowledged  in  the  Note  on  Sources, 
but  doubtless  I  have  not  listed  every  one.  I  am  grateful  to  all  who  took 
time  from  their  schedules  to  enhance  my  understanding  of  this  disease. 

Special  thanks  are  due  to  Carolyn  Brown's  staff  at  the  NIH  library, 
who  filled  an  astronomical  number  of  requests  for  copies  of  papers 
and  interhbrary  loan  books.  Betty  Murgolo,  especially,  went  to  great 
lengths  to  locate  obscure  but  key  sources.  John  Parascandola,  chief  of 
the  History  of  Medicine  Division,  National  Library  of  Medicine,  and 
his  staff,  especially  the  curator  of  modern  manuscripts,  Peter  Hirtle, 
also  proved  most  helpful  in  suggesting  relevant  documents  from  their 
rich  manuscript  collections.  Lois  South  in  the  Judicial,  Fiscal,  and  Social 
Branch  of  the  National  Archives  and  Records  Administration  provided 
knowledgeable  guidance  to  records  in  the  collections  of  the  U.S.  Public 
Health  Service  and  of  the  NIH.  Archivists  and  librarians  at  the  Mon- 
tana State  Archives  in  Helena,  Montana,  and  at  the  Renne  Library  of 
Montana  State  University  in  Bozeman,  Montana,  facilitated  my  search 
through  their  holdings.  Archivist  Richard  Popp  in  the  Department  of 
Special  Collections,  Joseph  Regenstein  Library,  University  of  Chicago, 
kindly  assisted  me  in  obtaining  copies  of  the  Howard  Taylor  Ricketts 
Papers.  Carolyn  Kopp,  university  archivist  at  the  Rockefeller  Univer- 
sity, similarly  provided  key  materials  from  the  Hideyo  Noguchi  Papers. 
Citations  from  these  collections  are  used  by  permission  of  the  Uni- 
versity of  Chicago  and  of  the  Rockefeller  University. 

Because  of  the  key  role  of  the  Rocky  Mountain  Laboratory  in  spotted 
fever  research  throughout  the  twentieth  century,  I  made  extensive  use 
of  materials  held  at  the  RML  library  and  at  the  Ravalli  County  His- 
torical Society.  Many  people  in  the  Bitterroot  Valley  told  me  of  their 
experiences  and  suggested  other  sources  of  information,  but  four  peo- 
ple in  Hamilton  extended  extraordinary  assistance.  Erma  Owings, 
archivist  at  the  Ravalli  County  Historical  Society,  helped  in  numerous 
ways  as  I  researched  this  remarkable  collection  of  county  documents. 
William  L.  Jellison,  a  retired  entomologist  from  the  laboratory,  active 
local  historian,  and  curator  of  spotted  fever  artifacts,  led  me  to  records 
he  had  preserved  from  destruction,  showed  me  historically  important 


Freface 


XV 


sites  in  the  valley,  introduced  me  to  many  long-term  residents  who 
remembered  the  early  days  of  spotted  fever,  and  made  helpful  sugges- 
tions for  improving  the  manuscript.  Robert  N.  Philip,  a  former  epi- 
demiologist at  the  laboratory,  offered  me  his  encyclopedic  know^ledge 
of  w^estern  Montana  and  the  fruits  of  his  ow^n  extensive  research  on 
spotted  fever.  His  criticism  of  the  manuscript  proved  invaluable.  Fi- 
nally, Leza  S.  Hamby,  Hbrarian  at  the  laboratory,  not  only  filled  my 
every  request  for  information  but  also  made  arrangements  for  me  to 
see  firsthand  a  dipping  vat  used  to  combat  spotted  fever  early  in  the 
century.  In  addition,  she  alw^ays  extended  warm  hospitality  during  my 
research  trips  to  the  valley. 

Among  the  numerous  scientists  and  physicians  to  whom  I  accrued 
debts,  special  thanks  must  go  to  all  whom  I  interviewed.  Named  in 
the  Note  on  Sources,  these  people  often  became  my  patient  teachers 
as  I  struggled  to  master  a  portion  of  the  intricacies  of  microbiology, 
entomology,  and  immunology.  Another  dimension  was  added  to  my 
research  when  David  H.  Walker,  then  in  the  Department  of  Pathology 
at  the  University  of  North  Carolina,  School  of  Medicine  at  Chapel 
Hill,  and  now  chairman  of  the  Pathology  Department  at  the  University 
of  Texas  Medical  Branch  at  Galveston,  introduced  me  to  the  group  of 
researchers  in  Palermo,  Sicily,  who  are  investigating  Rocky  Mountain 
spotted  fever's  rickettsial  relative,  boutonneuse  fever.  During  a  trip  I 
made  to  Italy  for  a  related  research  project,  Serafino  Mansueto,  Giu- 
seppe Tringali,  and  Vittorio  Scaffidi  extended  hospitaHty,  recounted 
their  research  strategies,  and  made  it  possible  for  me  to  observe  a  case 
of  boutonneuse  fever. 

Once  written,  the  manuscript  received  critical  review  from  a  variety 
of  scientists  and  historians.  Willy  Burgdorfer,  Eugene  P.  Campbell, 
James  A.  Cassedy,  Alan  M.  Cheever,  Robert  Edelman,  William  Jordan, 
Richard  A.  Ormsbee,  Margaret  Pittman,  Norman  H.  Topping,  David 
H.  Walker,  and  Charles  L.  Wisseman,  Jr.,  read  one  or  more  chapters. 
Saul  Benison,  William  L.  Jellison,  David  B.  Lackman,  Robert  N.  Philip, 
and  James  Harvey  Young  read  the  entire  manuscript.  I  am  greatly 
indebted  to  each  of  them,  whose  suggestions  significantly  improved 
the  accuracy  and  clarity  of  the  book.  Any  errors  that  remain  are  mine 
alone. 

I  must  also  gratefully  acknowledge  many  other  members  of  the 
NIAID  and  NIH  staffs  in  Bethesda  who  extended  themselves  to  assist 
me  in  various  ways.  Mary  Ann  Guerra  provided  essential  administra- 
tive support  throughout  the  project.  Patricia  Randall  and  her  associates 
in  the  NIAID  Public  Information  Office,  especially  Karen  Leighty  and 
Judy  Murphy,  proved  most  knowledgeable  about  recent  institute  his- 


xvi 


Preface 


tory  and  directed  my  attention  to  many  internal  files  and  pictures. 
Rurik  Fredrickson,  Harriet  R.  Greenwald,  and  Rhoda  Laskin  provided 
technical  assistance  during  the  course  of  the  project.  Rochelle  Howard 
prepared  computerized  files  of  NIAID  rickettsial  grants  and  of  a  col- 
lection of  photographs  relating  to  this  project.  Joanie  Shariat  vetted 
the  manuscript  with  skill  and  tact. 

Once  in  production,  the  book  received  careful  attention  from  several 
members  of  the  staff  at  Johns  Hopkins  University  Press.  Particularly 
I  would  like  to  thank  executive  editor  Henry  Y.  K.  Tom  for  his  support 
and  patience  in  bringing  this  manuscript  to  publication. 

Finally,  I  am  grateful  to  my  family,  who  never  failed  in  their  en- 
couragement of  this  project,  even  when  my  research  files  and  draft 
manuscripts  threatened  to  engulf  the  house.  My  husband,  Robert  L. 
Berger,  proved  to  be  an  excellent  research  assistant  as  well  as  my  first 
critical  reader  and  a  continuous  source  of  moral  support. 


Chapter  One 


A  Twentieth-Century 
Disease  of  Nature 

The  unwritten  history  of  the  investigational  work  in  connection  with  Rocky 
Mountain  spotted  fever,  if  written,  would  read  like  a  romance. 

William  Forlong  Cogswell,  ca.  1930 


Some  diseases  have  been  known  to  human  beings  for  eons.  Epilepsy, 
for  example,  was  well  recognized  by  the  ancients,  who  called  it  the 
falling  sickness  because  of  its  sudden  seizures.  Other  diseases  are  quite 
new,  acquired  immunodeficiency  syndrome,  or  AIDS,  being  perhaps 
the  most  recent  example.  Many  diseases  have  come  into  or  gone  out 
of  existence  according  to  conceptual  models  that  guided  the  medical 
communities  of  specific  societies.  Dropsy  was  a  recognized  clinical 
entity  in  the  eighteenth  century,  but  today  it  no  longer  exists  as  a 
distinct  disease,  its  swelling  of  the  tissues  being  viewed  rather  as  a 
symptom  of  several  different  pathological  conditions.  Rocky  Mountain 
spotted  fever,  the  subject  of  this  book,  may  thus  be  termed  a  twentieth- 
century  disease.  It  was  not  recognized  as  a  distinct  clinical  entity  until 
just  before  the  turn  of  the  century,  and  nearly  all  of  the  efforts  to 
understand  and  combat  it  have  been  made  within  this  century. 

Rocky  Mountain  spotted  fever  is  one  of  a  group  of  maladies  known 
as  diseases  of  nature.  The  pathogenic  organisms  that  cause  these  ill- 
nesses normally  inhabit  ticks,  mites,  fleas,  mosquitoes,  small  rodents, 
and  other  wild  animals.  Malaria  and  bubonic  plague  are  two  other 
well-known  members  of  this  group.  Human  beings  are  usually  acci- 
dental intruders  into  the  natural  cycles  of  these  organisms  that  oth- 
erwise exist  silently  in  nature.  Because  human  beings  are  not  a  part 
of  the  organisms'  biosystems,  moreover,  they  often  suffer  more  severely 
from  infections  of  this  group  than  do  arthropod  and  mammaUan  hosts. 

One  subgroup  of  the  diseases  of  nature  is  known  today  as  the 
rickettsial  diseases.  They  are  caused  by  extremely  small  bacteria  that 
have  the  peculiar  characteristic  of  conducting  their  life  processes  inside 
the  cells  of  their  hosts— a  property  more  generally  associated  with 
viruses.  Measured  in  microns,  a  unit  equal  to  one  ten-thousandth  of 


I 


2 


Rocky  Mountain  Spotted  Fever 


a  centimeter,  rickettsiae  take  on  three  primary  forms:  spheres  about 
0.3  microns  in  diameter;  short  rods  0.3  by  i.o  microns  long;  and  thin 
rods  about  2.0  microns  long.  In  contrast,  the  cholera  vibrio  measures 
1.5—5  microns  long,  and  the  rods  of  the  anthrax  bacillus,  the  first 
pathogenic  bacterium  identified  because  of  its  large  size,  are  5-10 
microns  long.^  The  rickettsiae  of  spotted  fever  normally  inhabit  ticks, 
those  of  murine  typhus  hve  in  fleas,  and  the  agents  of  rickettsialpox 
and  tsutsugamushi  are  found  in  mites.  Only  one  of  the  rickettsial 
diseases,  in  fact,  has  adapted  to  human  beings  as  its  hosts,  and  it  is 
transmitted  from  one  infected  person  to  another  via  the  body  louse. 
This  disease  is  classic,  epidemic  typhus,  which  is  also  notew^orthy  as 
the  only  rickettsial  disease  recognized  in  the  western  world  long  before 
the  twentieth  century.^ 

As  the  rickettsial  diseases  were  differentiated,  they  were  divided  into 
three  groups:  the  typhus  group,  the  spotted  fever  group,  and  the  tsutsu- 
gamushi group,  the  last  being  a  single  disease  hmited  to  Asia  and  the 
Pacific  islands.  In  addition,  diseases  known  as  Q  fever  and  trench  fever 
have  generally  been  associated  with  the  rickettsial  diseases,  but  each 
has  exhibited  sufficient  differences  from  the  other  rickettsial  diseases 
to  be  classified  in  a  separate  genus.  Members  of  the  spotted  fever 
group,  which  includes  Rickettsia  rickettsii,  the  organism  that  causes 
Rocky  Mountain  spotted  fever,  are  responsible  for  similar  but  not 
identical  diseases  scattered  across  the  world.  All  are  transmitted  by 
ticks,  except  for  the  rickettsia  that  causes  rickettsialpox,  a  mild,  mite- 
borne  disease  that  was  initially  confused  with  chickenpox.  Each  spotted 
fever  group  rickettsia,  moreover,  seems  to  have  evolved  its  distinc- 
tiveness as  have  many  animals  and  plants— through  geographical  iso- 
lation—for these  organisms  are  found  in  "islands"  of  infection  in 
particular  locations.  As  one  early  researcher  noted,  "spotted  fever  is 
a  'place'  disease,  being  definitely  hmited  to  a  certain  locality."^ 

In  widespread  areas  of  Africa,  in  India  and  Southeast  Asia,  and  in 
regions  of  Europe  and  the  Middle  East  adjacent  to  the  Mediterranean, 
Black,  and  Caspian  sea  basins,  close  relatives  of  R.  rickettsii,  most 
commonly  Rickettsia  conorii,  cause  relatively  benign  diseases  similar 
to  spotted  fever.  The  names  given  these  diseases  also  reflect  the  localities 
where  they  are  known:  Marseilles  fever,  South  African  tick  typhus, 
Kenya  tick  typhus,  and  Indian  tick  typhus.  Another  member  of  the 
group,  Rickettsia  sibirica,  produces  a  similarly  mild  disease,  usually 
known  as  North  Asian  tick  typhus  or  Siberian  tick  typhus.  Its  habitats 
are  Siberia  and  many  of  the  Asiatic  republics  of  the  Soviet  Union, 
various  islands  of  the  Sea  of  Japan,  Mongolia,  Pakistan,  and  possibly 
Czechoslovakia.  One  other  geographic  area  in  which  a  closely  related 


A  Twentieth -Century  Disease  of  Nature 


3 


disease  is  known  to  exist  is  the  Queensland  area  of  Australia.  Caused 
by  Rickettsia  australis,  this  type  of  spotted  fever  is  known  as  Queens- 
land tick  typhus. 

Rocky  Mountain  spotted  fever  itself  may  be  said  to  be  an  all- Amer- 
ican disease,  because  its  causative  organism  is  found  only  in  the  western 
hemisphere— North,  South,  and  Central  America.  Transmitted  by  sev- 
eral different  ticks  that  flourish  in  each  ecological  area,  R.  rickettsii 
causes  a  disease  that  has  been  known  by  the  local  names  Sao  Paulo 
typhus,  Tobia  petechial  fever,  Choix  fever,  American  spotted  fever, 
and  New  World  spotted  fever.  Because  it  was  first  identified  in  the 
Rocky  Mountain  region  of  North  America,  however,  its  oldest  ap- 
pellation was  Rocky  Mountain  spotted  fever.  Later,  when  it  was  rec- 
ognized in  other  areas  of  the  hemisphere,  many  scientists  argued  that 
such  a  provincial  designation  should  be  replaced  with  a  more  precise 
name,  such  as  tick-borne  typhus,  but  their  proposals  came  too  late. 
The  name  of  the  disease  had  become  fixed  in  both  public  and  medical 
minds,  despite  the  unfortunate  consequence  that  the  risk  of  infection 
outside  the  Rocky  Mountain  region  was  thus  masked.  Recognized  in 
the  United  States,  western  Canada,  western  and  central  Mexico,  Brazil, 
Colombia,  Panama,  and  Costa  Rica,  spotted  fever  varies  in  virulence 
from  place  to  place.  The  reason  for  this  variation  remains  unknown. 
Spotted  fever  may  exact  a  mortality  as  high  as  70  percent  or  as  low 
as  5  percent.  On  an  average,  if  left  untreated,  it  will  kill  just  over  20 
percent  of  its  victims.  Of  all  infectious  diseases,  spotted  fever  is  one 
of  the  most  severe,  and  it  ranks  as  the  most  perilous  of  all  rickettsial 
infections  in  the  United  States."^ 

Victims  of  Rocky  Mountain  spotted  fever  display  variations  of  a 
closely  related  set  of  symptoms.  A  week  or  two  after  the  patient  has 
been  bitten  by  a  tick,  the  disease  begins  to  manifest  itself.  The  onset 
may  be  sudden  or  may  be  preceded  by  a  few  days  of  general  malaise, 
after  which  the  symptoms  become  more  dramatic.  The  first  sign  is 
often  a  splitting  headache— frequently  described  as  the  worst  ever 
encountered  by  the  victim— accompanied  by  pains  in  the  back,  joints, 
and  legs.  Light  is  painful  to  the  eyes,  and  a  stiff  neck  sometimes  leads 
physicians  to  suspect  meningitis.  The  spotted  fever  victim's  temperature 
rises  rapidly  to  102°  to  104°  R  The  patient  is  usually  restless,  cannot 
sleep  well,  and  frequently  suffers  from  periods  of  delirium.  Occasion- 
ally, the  initial  symptoms  of  spotted  fever  may  mimic  appendicitis  or 
the  common  cold,  making  diagnosis  difficult. 

As  the  infection  progresses,  the  rickettsial  organisms  multiply  within 
the  endothelial  cells  that  line  the  victim's  capillaries.  These  cells  even- 
tually swell,  some  burst,  and  by  the  third  or  fourth  day  of  recognizable 


The  rash  of  Rocky  Mountain  spotted  fever  covers  the  entire  body,  includ- 
ing the  palms  of  the  hands  and  the  soles  of  the  feet.  Because  so  few  diseases 
exhibit  such  an  extensive  rash,  it  is  considered  diagnostic  in  conjunction 
with  high  fever  and  history  of  exposure  to  ticks.  (Courtesy  of  Eugene  P. 
Campbell  and  used  by  permission  of  Norman  H.  Topping.) 


illness,  blood  begins  to  seep  through  tiny  holes  in  the  capillary  walls. 
These  hemorrhages  cause  the  characteristic  spots  of  the  disease,  which 
often  look  like  the  rash  of  measles  and  can  be  felt  as  slightly  raised 
areas  under  the  skin.  They  appear  first  on  the  wrists  and  ankles, 
spreading  later  to  the  limbs,  the  trunk  and  the  face.  Unlike  the  rash 
of  some  other  rickettsial  diseases,  the  spots  of  Rocky  Mountain  spotted 
fever  often  appear  on  the  palms  of  the  hands  and  the  soles  of  the  feet. 
Since  only  a  few  diseases  produce  this  symptom,  it  is  often  considered 
a  definitive  diagnostic  sign. 

If  left  untreated,  most  patients  will  recover  from  their  illness  within 
two  weeks.  Just  over  20  percent,  however,  especially  people  over  forty 
years  old  and  those  with  existing  medical  problems,  will  die  from  their 
infections.  In  a  few  cases,  the  disease  is  fulminant,  killing  its  victim 
within  a  few  days  of  onset,  often  before  the  characteristic  rash  has 
appeared. 

That  Rickettsia  rickettsii  is  so  well  adapted  to  life  in  its  tick  host 
indicates  a  symbiotic  relationship  that  has  evolved  over  eons.  This 


A  Twentieth -Century  Disease  of  Nature 


5 


suggests  that  spotted  fever  probably  struck  human  victims  long  before 
it  was  distinguished  as  a  separate  disease.  Recently,  in  fact,  William 
D.  Tigertt  has  argued  that  a  1759  epidemic  in  North  Carolina  was 
probably  caused  by  Rocky  Mountain  spotted  fever/  Civil  War  diaries 
also  contain  some  references  to  afflictions  that  may  have  been  spotted 
fever,  such  as  seasonal  occurrences  of  "black  measles"  chronicled  by 
a  nurse  stationed  near  Cairo,  Illinois.^  Because  Rocky  Mountain  spot- 
ted fever  remained  undifferentiated  from  other  fevers  identified  by 
similar  names  and  symptoms  until  the  late  nineteenth  century,  however, 
historical  inquiry  into  earlier  periods  is  limited  to  speculation.  The 
story  of  Rocky  Mountain  spotted  fever  may  thus  be  said  to  begin  with 
the  description  of  a  peculiar  affliction  recorded  by  pioneers  traversing 
the  trails  across  the  North  American  west.  Research  on  the  disease 
certainly  had  its  origins  in  a  single  place,  the  Bitterroot  Valley  of 
Montana. 

Although  Rocky  Mountain  spotted  fever  was  not  identified  until 
just  before  the  twentieth  century  began,  its  louse-borne  relative,  epi- 
demic typhus  fever,  had  plagued  European  populations  for  centuries. 
Almost  always  Hnked  to  conditions  of  human  misery,  typhus  was 
known  to  accompany  prisoners,  sailors,  armies,  and  refugees— popula- 
tions who,  during  cold  weather,  were  likely  to  wear  the  same  clothing 
day  and  night  for  weeks  on  end  because  of  poor  hygienic  conditions. 
Because  a  widespread  body  rash,  which  does  not  spread  to  the  face, 
also  accompanies  typhus,  it,  too,  was  often  called  spotted  fever.  In  this 
book,  however,  I  employ  that  term  only  as  a  synonym  for  Rocky 
Mountain  spotted  fever. 

Before  I  commence  the  story  of  Rocky  Mountain  spotted  fever,  a 
brief  digression  to  review  the  history  of  epidemic  typhus  fever  may  be 
helpful,  especially  in  understanding  why  spotted  fever  was  not  iden- 
tified as  a  distinct  disease  until  the  end  of  the  nineteenth  century. 
Hippocrates  applied  the  word  typhus^  from  the  Greek  word  meaning 
"smoky"  or  "hazy,"  to  confused  or  stuporous  states  of  mind  frequently 
associated  with  high  fevers.  Accounts  of  ancient  plagues,  however,  do 
not  differentiate  typhus  from  other  epidemic  fevers.  The  first  descrip- 
tions of  a  disease  that  closely  resembled  typhus  appeared  near  the  end 
of  the  fifteenth  century.  In  1489-90,  during  the  civil  wars  of  Granada, 
Spanish  physicians  described  a  typhus-like  disease  that  killed  seventeen 
thousand  Spanish  soldiers— six  times  the  number  killed  in  combat  with 
the  Moors.  In  the  early  sixteenth  century,  a  similar  malady  appeared 
among  armies  arrayed  in  Italy  and  in  the  Balkans.  In  1546,  Girolamo 
Fracastoro  (Fracastorius),  who  had  observed  the  Itafian  epidemics, 
pubhshed  the  first  clear  description  of  what  he  termed  a  "lenticular 


6 


Rocky  Mountain  Spotted  Fever 


or  punctate  or  petechial"  fever  also  characterized  by  headache  and 
general  malaise.  Toward  the  end  of  the  sixteenth  century,  typhus  was 
also  recorded  in  the  Mexican  highlands,  where  it  killed  more  than  two 
miUion  Indians.  It  remains  unclear,  however,  whether  the  disease  was 
brought  to  the  New  World  by  Spanish  explorers  or,  as  some  evidence 
indicates,  was  known  to  the  Aztecs  and  some  pre-Columbian  Indians 
in  Mexico.^ 

Typhus  rose  dramatically  in  early  nineteenth-century  Europe.  In 
1812,  Napoleon's  catastrophic  expedition  to  Russia  was  plagued  by 
typhus.  Between  18 16  and  18 19  a  great  epidemic  of  the  disease  struck 
seven  hundred  thousand  people  in  Ireland,  whose  population  was  only 
six  million.  For  several  more  decades,  however,  medical  understanding 
of  the  disease  remained  confused.  By  the  late  eighteenth  century,  the 
medical  nosologist  Boissier  de  Sauvages  had  begun  using  the  word 
typhus  to  describe  the  neurological  symptoms  of  a  particular  disease, 
but  few  attempts  were  made  to  distinguish  pathologically  between 
typhus  and  typhoid  fever,  which  also  displayed  a  red  rash.  Even  into 
the  twentieth  century,  the  link  between  typhoid  and  typhus  was  per- 
petuated in  nomenclature.  In  many  European  countries,  the  former 
was  known  as  typhus  abdominalis  and  the  latter  as  typhus  exanthe- 
maticus.^ 

During  the  first  half  of  the  nineteenth  century,  researchers  centered 
in  the  clinical  schools  of  Paris,  London,  Dublin,  and  Vienna  compiled 
detailed  histories  of  diseases,  which  were  correlated  with  gross  path- 
ological lesions  at  autopsy.  By  this  method  they  were  able  to  distinguish 
more  precisely  among  afflictions  sharing  similar  symptoms,  such  as 
the  many  types  of  fevers  from  which  people  suffered.^  In  1837  a 
Philadelphia  physician,  WiUiam  Wood  Gerhard,  who  had  studied  the 
distinctive  intestinal  lesions  of  typhoid  as  a  student  of  Pierre  Louis  in 
Paris,  noted  their  absence  in  victims  of  typhus  fever,  which  had  been 
epidemic  in  Philadelphia  the  previous  year.  Gerhard's  work,  however, 
was  not  immediately  embraced  by  physicians  who  clung  to  older  the- 
ories of  the  unity  of  fevers.  It  was  not  until  mid  century  that  additional 
pathological  and  epidemiological  research,  especially  by  William  Jen- 
ner  and  Austin  Flint,  convinced  most  American  physicians  that  indeed 
typhus  and  typhoid  were  distinct  disease  entities. ^° 

The  European  revolutions  of  1848  spawned  typhus  epidemics  in 
Eastern  Europe,  as  did  African  warfare  in  Ethiopia.  During  a  partic- 
ularly severe  outbreak  of  typhus  in  Upper  Silesia,  the  German  physician 
and  politician  Rudolf  Virchow  published  a  radical  assessment  of  the 
epidemic  that  subsequently  cost  him  his  government  post.  Observing 
that  the  disease  afflicted  the  poor,  the  uneducated,  and  the  unclean, 


A  Twentieth -Century  Disease  of  Nature 


7 


Virchow  called  for  democracy,  education,  and  public  health  measures 
as  the  proper  "treatment"  of  the  epidemic.  Although  Virchow  argued 
strongly  for  social  reform  as  a  means  to  benefit  health,  he  also  was  in 
the  vanguard  of  German  scientists  who  believed  that  medicine  would 
benefit  from  laboratory  investigations.  In  research  aided  by  improved 
microscopes,  Virchow  and  other  scientists  focused  on  pathological 
changes  in  the  tissues  and  cells  to  study  the  disease  process. 

During  the  last  quarter  of  the  nineteenth  century,  such  laboratory 
research  culminated  in  the  work  of  French  chemist  Louis  Pasteur, 
German  physician  Robert  Koch,  and  their  associates,  who  identified 
specific  microorganisms  as  the  causes  of  particular  infectious  diseases. 
This  new  germ  theory,  when  linked  with  the  pathological  changes 
documented  for  particular  diseases,  revolutionized  the  way  physicians 
conceptualized  infectious  diseases.  It  also  provided  a  framework  in 
which  rapid  advances  could  be  made  in  understanding  afflictions  such 
as  typhus.  Corollaries  of  the  germ  theory,  which  explained  how  mi- 
croorganisms were  transmitted,  provided  a  basis  for  active  intervention 
programs  to  prevent  diseases.  Purifying  water  supplies  reduced  the 
incidence  of  waterborne  diseases,  for  example.  Crusades  against  insect 
vectors  were  also  mounted  to  control  such  diseases  as  malaria  and 
yellow  fever. 

Rocky  Mountain  spotted  fever  was  identified  as  a  disease  with  symp- 
toms and  a  clinical  course  distinct  from  other  fevers  just  as  the  germ 
theory  was  making  its  way  across  the  Atlantic  from  Europe.  Even 
though  many  American  physicians  and  lay  persons  remained  skeptical 
about  the  new  theory,  their  response  to  diseases  such  as  spotted  fever 
was  informed,  if  not  initially  guided,  by  its  constructs.  During  ensuing 
decades,  the  germ  theory  transformed  medical  practice,  fostered  the 
growth  of  an  international  medical  research  establishment  with  its 
own  professional  dynamic,  and  established  principles  on  which  in- 
vestigational efforts  were  conducted.  Furthermore,  it  furnished  a  con- 
text for  lay  persons  to  think  about  infectious  diseases  and  altered  their 
views  of  the  role  of  governments  in  medical  matters.  In  approaching 
the  history  of  Rocky  Mountain  spotted  fever,  one  must  seek  to  un- 
derstand the  interactions  between  these  broad  trends  and  the  expe- 
rience of  society  with  a  single  disease.  What  role  did  the  profession- 
alization  of  science  throughout  the  world  play  in  strategies  to 
understand  and  combat  this  disease?  What  can  the  experience  with 
spotted  fever  tell  us  about  the  process  of  scientific  discovery  and  ap- 
pUcation?  How  did  communities  respond  to  the  presence  of  this  disease 
in  their  midst?  What  role  did  they  expect  their  governments  to  play, 
and  how  effective  was  political  action  against  the  disease? 


8 


Rocky  Mountain  Spotted  Fever 


The  history  of  Rocky  Mountain  spotted  fever  may  thus  serve  as  a 
lens  through  which  we  can  view  twentieth-century  thought  regarding 
infectious  diseases  and  the  apphcation  of  new  concepts  to  research, 
diagnosis,  prevention,  and  treatment.  One  of  the  early  Montana  leaders 
in  the  effort  to  combat  spotted  fever,  quoted  in  the  epigraph  to  this 
chapter,  asserted  that  the  story  of  research  on  spotted  fever  should 
read  like  a  romance.  In  the  following  pages,  I  hope  that  some  of  the 
romance  may  be  evident  as  well  as  an  increased  understanding  of  how 
science,  medicine,  and  society  in  the  twentieth  century  have  responded 
to  one  particular  disease  of  nature. 


Chapter  Two 


A  Blight  on  the 
Bitterroot 

Charles  Draper,  25  years,  of  Kendall's  lumber  camp  on  the  westside  died  at 
the  Sisters  Hospital  on  April  4  of  that  dread  disease  spotted  fever,  after  a 
few  days'  illness. 

Obituary,  Northwest  Tribune,  1901 


The  curved  western  border  of  the  state  of  Montana  somewhat  re- 
sembles the  profile  of  an  Indian  brave.  Thrusting  into  the  Idaho  pan- 
handle like  the  nose  of  that  brave  is  the  spectacular  Bitterroot  Valley.^ 
Protected  from  the  full  force  of  winter  storms  by  the  rugged  Bitterroot 
Mountains  on  the  west  and  the  more  gentle  Sapphire  range  to  the  east, 
the  valley's  flat  bottomlands  are  the  remains  of  an  ancient  lake  whose 
beaches  remain  visible  as  bench  lands  on  either  side.  Through  the 
valley,  which  stretches  approximately  one  hundred  miles  long  and 
from  eight  to  ten  miles  wide  at  an  average  elevation  of  thirty-five 
hundred  feet  above  sea  level,  the  Bitterroot  River  flows  from  south  to 
north  into  the  Clark's  Fork  of  the  Columbia  River  near  Missoula.  Not 
far  away  is  the  so-called  Yellowstone  hot  spot,  where  the  earth's  molten 
interior  rises  close  to  the  surface,  producing  geysers,  hot  springs,  and 
boiling  mud.  Although  less  geologically  active  than  Yellowstone,  the 
Bitterroot  Valley  became  known  as  a  medical  hot  spot  just  before  the 
twentieth  century  began.  It  was  here  that  a  mysterious  disease,  virulent 
Rocky  Mountain  spotted  fever,  claimed  many  lives  and  challenged 
researchers  seeking  to  solve  its  riddle  to  formulate  new  concepts  about 
the  nature  of  infectious  diseases. 

Until  the  last  quarter  of  the  nineteenth  century,  there  were  no  ac- 
counts of  any  unusual  disease  in  the  Bitterroot,  whose  invigorating 
cHmate  attracted  first  Indian  and  later  white  inhabitants.^  The  Salish, 
or  Flathead,  Indians,  who  lived  in  the  valley  and  ate  the  bitter  roots 
of  a  pink  spring  wildflower  from  which  the  valley  took  its  name, 
reported  no  special  local  affliction.  Like  most  primitive  peoples,  the 


9 


lO 


Rocky  Mountain  Spotted  Fever 


Salish  interpreted  disease  as  a  magicoreligious  process,  in  which  a 
malevolent  spirit,  acting  on  its  own  or  at  the  behest  of  an  enemy  of 
the  sick  person,  brought  suffering.^  The  Indians  did  not  make  detailed 
diagnostic  observations  that  could  be  used  later  as  medical  evidence, 
and  their  oral  tradition  precluded  written  records  in  any  case. 

Before  the  arrival  of  whites,  the  Salish,  like  most  other  American 
Indians,  were  remarkably  healthy.  They  were  free  from  most  diseases 
caused  by  airborne  microorganisms  because  the  cold,  dry  air  of  Mon- 
tana was  inimical  to  airborne  bacteria.  Contagious  diseases  such  as 
smallpox,  diphtheria,  scarlet  fever,  measles,  and  venereal  ailments, 
which  ravaged  European  cities,  did  not  touch  them.  Since  accidents 
and  wounds  sustained  in  warfare  were  common,  however,  the  Salish 
had  developed  competency  in  setting  fractures.  Intestinal  problems  and 
rheumatic  complaints,  of  which  there  were  many,  were  usually  treated 
by  sweat  baths  or  plunges  into  icy  streams;  sometimes  a  combination 
of  these  methods  was  used.  Among  Sahsh  traditions  was  a  general 
spring  warning  against  entering  certain  canyons  in  the  Bitterroot  said 
to  be  inhabited  by  evil  spirits.  After  the  identification  of  virulent  spotted 
fever,  this  admonition  suggested  that  the  Salish  might  have  been  fa- 
miliar with  the  disease,  but  later  Indian  testimony  failed  to  confirm 
this.  One  of  the  earliest  reports  on  spotted  fever  noted  that  "no  au- 
thentic information"  could  be  obtained  linking  the  Indian  superstition 
to  the  disease,  "though  many  old  residents,  including  Indians,  white 
trappers,  traders,  and  Catholic  priests  were  consulted.'"^ 

Accounts  of  the  periodic  visits  of  non-Indians  in  the  valley  during 
the  early  nineteenth  century,  furthermore,  are  notable  for  the  absence 
of  any  mention  of  a  deadly  disease.  The  most  famous  early  visitors 
were  members  of  the  Lewis  and  Clark  expedition,  who  traversed  the 
valley  in  September  1805.  Before  embarking  on  their  journey,  Meri- 
wether Lewis  and  William  Clark  had  been  given  medical  instruction 
by  respected  physicians,  including  the  distinguished  Benjamin  Rush. 
The  explorers  were  advised  to  pay  special  attention  to  the  health  of 
the  Indians  they  encountered.^  They  recorded  the  presence  of  trachoma 
among  the  Columbia  River  Indians  and  the  "calamity  of  bHndness" 
that  had  resulted  from  this  disease.^  When  they  traveled  through  the 
Bitterroot,  however,  camping  near  the  later  towns  of  Grantsdale  and 
Stevensville,  the  explorers  did  not  record  the  presence  of  any  feared 
local  malady.  In  September  the  wood  ticks  that  carry  spotted  fever  are 
in  estivation,  or  "summer  hibernation,"  hence  Lewis  and  Clark  were 
not  at  great  risk.  On  the  return  trip  of  the  expedition  the  following 
year,  Clark  revisited  the  Bitterroot  in  early  July  — a  time  during  which 
some  ticks  would  probably  still  be  active— while  Lewis  returned  to 


A  Blight  on  the  Bitterroot 


II 


Saint  Louis  across  northern  Montana.  Clark's  path  wound  through 
the  section  of  the  Bitterroot  where  spotted  fever  was  later  shown  to 
be  most  prevalent,  yet  he  reported  no  unusual  occurrences.  The  ex- 
periences of  Lewis  and  Clark  in  the  Bitterroot  suggest  three  alternative 
scenarios  with  regard  to  spotted  fever  in  the  early  nineteenth  century: 
first,  at  this  time  virulent  spotted  fever  was  not  widely  spread  through 
the  Bitterroot;  second,  the  disease  existed,  but  its  tick  vectors  were  in 
estivation  during  both  visits;  and  third,  Lewis  and  Clark  were  simply 
lucky  not  to  encounter  the  deadly  fever. 

For  several  decades  after  Lewis  and  Clark's  expedition,  few  other 
white  visitors  came  to  the  Bitterroot.  The  number  of  travelers  to  other 
western  areas  was  stimulated  by  the  Mormon  immigration  to  Utah  in 
1847  and  the  discovery  of  the  CaHfornia  goldfields  two  years  later. 
Many  of  these  mid-century  settlers  and  prospectors  commented  on 
various  fevers  encountered  on  the  Oregon  Trail  in  Wyoming,  northern 
Utah,  and  southern  Idaho.  Bull  fever,  mountain  fever,  typho-malaria 
fever  of  the  Rocky  Mountains,  black  fever,  blue  disease,  and  spotted 
fever  were  all  names  reported.  Although  these  diseases  are  difficult  to 
diagnose  retrospectively,  some  may  have  been  cases  of  Rocky  Moun- 
tain spotted  fever.  Most  early  observers,  including  U.S.  Army  physi- 
cians stationed  at  outposts  in  the  region,  described  the  diseases  they 
encountered  in  terms  of  those  with  which  they  were  familiar  in  the 
east.  They  assumed  that  these  diseases  had  been  "altered  by  chmate 
and  altitude,"  changes  that  explained  unusual  clinical  pictures.^ 

The  first  whites  to  live  continuously  in  the  Bitterroot  Valley  were 
neither  prospectors  nor  settlers  but  rather  Jesuit  priests,  who  arrived 
in  1 84 1  at  the  request  of  the  Sahsh.  This  unusual  attraction  of  the 
Indians  to  white  religion  had  developed  through  the  Sahsh's  contact 
with  Canadian  Indians.  In  the  1820s  a  band  of  Iroquois  had  left  their 
homes  on  the  Saint  Lawrence  River  and  migrated  across  the  continent 
to  the  Bitterroot.  The  Salish  welcomed  the  Iroquois  as  friends,  even- 
tually intermarried  with  them,  and  rapidly  adopted  the  Roman  Cath- 
olic doctrines  that  the  Iroquois  had  learned  from  French  CathoHc 
priests  in  Canada.  During  the  1830s,  "a  desire  to  have  some  'Black 
Robes,'  in  their  midst"  took  possession  of  the  Salish.  Between  183 1 
and  1836,  they  dispatched  three  envoys  to  Saint  Louis  to  petition  the 
church  for  a  priest  to  be  sent  to  their  tribe.  This  request  was  granted 
in  1840,  and  the  following  year  two  Jesuit  missionaries,  Gregory  Men- 
garini  and  Pierre-Jean  DeSmet,  arrived  to  found  Saint  Mary's  Mission 
in  the  north  end  of  the  valley,  near  the  later  site  of  the  town  of 
Stevensville.  In  1845  ^  medically  trained  Jesuit,  Anthony  Ravalli,  was 
sent  to  serve  the  Indians  at  Saint  Mary's.  He  remained  for  five  years 


12 


Rocky  Mountain  Spotted  Fever 


until  Saint  Mary's  was  closed  in  1850  because  of  a  threatened  attack 
from  hostile  Indian  tribes.  In  1867,  the  year  after  the  mission  was 
reopened,  Ravalli  returned  and  expanded  his  medical  practice  to  in- 
clude white  settlers  who  had  migrated  to  the  valley  after  the  Civil  War. 
Father  RavaUi,  after  whom  was  named  the  county  in  which  most  of 
the  Bitterroot  Valley  lies,  was  one  of  very  few  physicians  available  to 
valley  residents  until  the  mid  1880s.  Many  stories  recount  Ravalli's 
self-sacrificing  medical  practice,  but  none  specifically  mentions  spotted 
fever  as  a  problem  with  which  he  dealt.^ 

During  the  sixteen  years  that  the  Jesuits  were  absent  from  the  valley 
between  1850  and  1866,  white  settlement  commenced.  As  the  priests 
departed,  John  Owen,  a  former  army  sutler  and  self-styled  major, 
leased  mission  property  for  the  construction  of  a  trading  post,  which 
was  quickly  dubbed  Fort  Owen  because  of  the  walled  stockade  sur- 
rounding it.  In  the  early  1860s,  when  gold  was  discovered  in  Montana, 
Owen  profited  from  the  sale  of  vegetables  and  flour  to  the  mining 
camps.  The  gold  rush  also  brought  new  settlers  into  Montana  and  the 
Bitterroot.  In  1864  the  brothers  Harry  and  James  Cohen  settled  in  the 
valley  with  their  wives,  who  became  the  first  white  women  to  establish 
residency  in  the  Bitterroot.^  During  the  next  decade  many  other  families 
arrived  and  helped  found  towns  along  the  river  that  resembled  pearls 
on  a  string.  Stevensville  and  Corvallis  were  estabUshed  in  1864  and 
1868,  respectively,  and  by  1880  there  were  more  than  a  thousand 
white  settlers  living  in  the  valley. Many  new  residents  were  probably 
seeking  to  avoid  the  social  upheavals  caused  by  the  Civil  War  and 
Reconstruction,  for  a  significant  portion  of  them  came  from  Kentucky, 
Georgia,  and  the  Carolinas.  Others  migrated  from  Missouri,  Quebec, 
and  New  Brunswick.  These  early  settlers  produced  grain,  engaged  in 
lumbering  on  a  small  scale,  and  experimented  with  fruit  orchards, 
especially  apples.  The  first  fruit  trees  were  apparently  planted  in  1866, 
and  after  1870,  under  the  leadership  of  the  brothers  W.  E.  and  D.  C. 
Bass,  apples  became  a  commercial  crop.^^ 

The  increasing  use  of  land  in  the  Bitterroot  for  these  economic 
pursuits  eventually  produced  discord  with  the  hunting-gathering  way 
of  life  of  the  Salish.  In  1871,  President  Ulysses  S.  Grant  ordered  that 
the  Sahsh,  along  with  the  Nez  Perce  Indians  who  migrated  annually 
through  the  valley,  be  removed  to  the  Jocko  Reservation  in  northern 
Montana.  The  following  year.  General  James  A.  Garfield  negotiated 
a  treaty  to  this  effect  with  two  of  the  three  Salish  chiefs.  Chief  Chariot, 
son  of  Victor,  for  whom  one  of  the  valley  towns  was  named,  refused 
to  sign.  He  won  the  right  to  remain  in  the  Bitterroot  until  his  death, 
but  he  and  his  followers  were  expected  to  live  on  small  grants  of  land 


n 

-0 


r-  t:^ 


T 


\ 


0 


^  I)  0 


Retrospective  studies  in  the  early  twentieth  century  revealed  that  spotted 
fever  had  been  encountered  throughout  the  West  during  the  late  nineteenth 
century  by  prospectors  and  settlers.  This  map  shows  its  known  distribution 
about  1900.  (Courtesy  of  the  Rocky  Mountain  Laboratories,  NIAID.) 


14 


Rocky  Mountain  Spotted  Fever 


like  white  settlers.  The  Indians  were  not  successful  as  farmers,  hence 
in  1 89 1,  Chariot  decided  to  abandon  the  valley.  Accompanied  by  a 
hundred  other  Salish  who  had  remained  in  the  valley,  Chariot  moved 
to  the  reservation,  leaving  the  Bitterroot  Valley  wholly  in  the  hands 
of  whites. 

During  this  transition  period,  the  white  population  of  the  Bitterroot 
swelled  as  construction  of  the  Northern  Pacific  Railroad  approached 
Missoula.  After  1880,  sawmills  sprang  up  to  supply  railroad  ties,  sheep 
were  grazed  on  the  east  side  of  the  valley,  and,  when  quartz  deposits 
were  discovered,  an  interest  in  mining  developed.  The  Northern  Pacific 
was  completed  to  Missoula  in  1883,  and  five  years  later  a  branch  line 
was  constructed  up  the  Bitterroot  as  far  as  Grantsdale.  As  opposed  to 
the  rough  wagon  road  along  the  river  in  1870,  the  railroad  provided 
businessmen  in  the  valley  an  efficient  conduit  for  transporting  their 
goods  to  market.  By  1890  there  were  eight  sawmills  in  constant  op- 
eration; two  flour  mills;  more  than  thirty- three  thousand  sheep  pro- 
ducing wool  for  shipment  to  commercial  markets;  a  growing  number 
of  quartz,  silver,  and  copper  mines;  and  more  than  one-hundred  thou- 
sand fruit  trees,  which  came  to  make  the  valley  known  as  the  apple 
center  of  Montana. 

Lumbering  operations  were  especially  active  during  this  period.  In 
1887,  for  instance,  one  lumber  mill  near  Lake  Como  was  cutting  ten 
thousand  feet  of  lumber  per  day,  and  by  1890,  one  near  Grantsdale 
produced  forty  thousand  feet  each  day.^'*  This  was  just  the  beginning 
of  the  boom,  however,  because  railroads,  mines,  and  other  markets 
had  an  insatiable  appetite  for  lumber.  Sawmills  provided  jobs  for 
hundreds  of  valley  residents,  and  the  bountiful  forests  of  the  Bitterroot 
seemed  to  offer  an  endless  supply  of  trees.  By  1896  lumbering  oper- 
ations in  the  valley  produced  some  sixty  to  seventy  million  feet  of 
lumber  each  year.^^ 

Much  of  this  massive  deforestation  took  place  on  the  west  side  of 
the  valley,  the  site  where  virulent  spotted  fever  was  contracted.  In 
recent  years  researchers  have  speculated  about  a  relationship  between 
the  denuding  of  the  valley's  trees  and  the  advent  of  virulent  spotted 
fever.  Robert  N.  Philip,  an  epidemiologist  formerly  at  the  Rocky  Moun- 
tain Laboratory,  has  compiled  extensive  records  about  the  history  of 
the  valley  and  the  occurrence  of  the  disease.  He  points  out  that  the 
incidence  of  spotted  fever  "was  vitally  related  to  timber  harvest  and 
the  opening  of  the  west  side  woodlands  to  grazing  and  unwanted  small 
mammal  and  tick  infestation."^^  The  scrub  vegetation  that  replaced 
the  forests  was  an  ideal  habitat  for  small  rodents  and  their  tick  par- 
asites. Humans  entering  this  area  consequently  ran  an  increased  risk 


A  Blight  on  the  Bitterroot 


15 


of  encountering  infected  ticks.  This  hypothesis  offers  a  logical  expla- 
nation for  the  apparently  sudden  appearance  of  the  disease  at  the  end 
of  the  century.  Speculation  about  why  spotted  fever  was  more  deadly 
in  the  Bitterroot  than  across  the  mountains  in  Idaho,  on  the  other 
hand,  focuses  on  a  possible  genetic  mutation  m  the  organism  but 
remains  a  mystery. 

In  1889,  Montana  was  granted  statehood,  and  expansion  in  the 
Bitterroot  continued  unabated.  Marcus  Daly,  the  copper  magnate  of 
the  Anaconda  Mining  Company,  bought  acreage  in  the  valley  for 
breeding  his  celebrated  race  horses.  In  1 890,  Daly  established  a  sawmill 
near  his  propert}'  and  founded  a  town  named  after  one  of  his  agents, 
James  W.  Hamilton,  for  the  mill  hands. ^"  Three  years  later  most  of 
the  Bitterroot  Valley  was  split  off  from  Missoula  County  and  named 
Ravalli  Count}'  after  the  venerated  physician-priest.  In  1898  the  Ravalli 
Count}^  seat  was  moved  from  its  original  site  in  Stevensville  to  Ham- 
ilton. 

As  the  population  of  the  Bitterroot  increased  during  these  two  dec- 
ades of  expansion,  so  did  its  need  for  medical  attention.  Some  phy- 
sicians had  moved  into  the  valley  after  1870,  but  w^ith  under  a  thousand 
people  scattered  over  its  one-hundred-mile  length,  few  stayed  for  very 
long,  because  a  doctor  had  to  engage  in  other  pursuits  as  well  as 
medicine  to  make  a  living. In  1880,  for  example,  the  Weekly  Mis- 
soulian  published  this  advertisement:  "A  good  physician  is  much 
needed  up  the  Bitter  Root  Valley.  There  are  probably  a  thousand  people 
on  the  Bitter  Root,  and,  save  the  venerable  Father  RavaUi,  there  is  no 
medical  advisor  the  whole  length  of  the  Valley.  It  strikes  us  that  a  man 
who  is  willing  to  do  a  little  farming  or  stock-raising  in  connection 
with  his  medical  practice  could  reap  a  harvest  in  this  localit)^  He  should 
be  a  young  man  and  willing  to  make  hard  rides  occasionally."^^ 

In  spite  of  the  difficult  conditions,  this  call  for  help  was  answered. 
By  1882  two  physicians  had  accepted  the  challenge  and  estabhshed 
practices  in  the  Bitterroot.  One  of  them,  R.  A.  Wells,  was  immediately 
charged  with  managing  a  smallpox  epidemic. In  1884,  Father  Ravalli 
died,  and  the  new^  doctors  who  took  his  place  assumed  the  arduous 
task  of  dealing  with  the  common  infectious  diseases  against  which  no 
successful  therapy  was  then  available.  In  1885,  for  example,  a  diph- 
theria epidemic  claimed  six  Hves  of  its  eight  reported  victims.  Between 
1883  and  1885,  fifn'-four  Indians  were  buried,  many  of  them  young 
people,  apparently  victims  of  tuberculosis.^^  Typhoid  was  a  recurring 
problem,  primarily  because  of  contaminated  water  at  sawmills  and 
mines.  Smallpox  epidemics  flared  annually  because  many  people  were 
not  vaccinated,  even  though  an  efficacious  vaccine  was  available. 


i6 


Rocky  Mountain  Spotted  Fever 


During  this  period  of  settlement  and  growth,  there  were  few  reports 
of  spotted  fever  cases.  Before  1895  newspapers  cited  fifteen  illnesses 
that  might  be  construed  as  spotted  fever,  and  a  later  official  survey 
noted  twenty-three  cases  certified  by  local  physicians. A  retrospective 
diagnosis  made  after  the  turn  of  the  century  marked  1873  as  the  year 
in  which  the  first  definite  case  of  the  disease  was  evident.  The  victim, 
identified  only  as  "J.W.,"  lived  near  Woodside  and  died  in  May  1873. 
Since  the  attending  doctor,  who  may  have  been  John  B.  Buker,  an 
Indian  agent  and  a  physician,  had  died  by  the  time  this  inquiry  was 
made,  diagnosis  was  on  the  basis  of  testimony  from  the  stricken  man's 
relatives  and  neighbors  who  had  seen  later  cases  of  the  disease. 
Reports  of  spotted  fever  deaths  first  appeared  in  local  newspapers  in 
1882  and  1883.  Diagnoses  in  these  cases  were  never  confirmed,  how- 
ever, and  they  may  in  fact  have  been  some  other  disease. 

Since  there  was  no  hospital  in  the  Bitterroot  until  1895,  valley 
physicians  transported  their  severely  ill  patients  to  Missoula.  In  1873 
a  French  Canadian  order  of  Roman  CathoHc  nuns,  the  Sisters  of  Char- 
ity of  Providence,  established  the  first  hospital  in  Missoula,  which  was 
officially  named  Saint  Patrick's  Hospital  but  commonly  called  Sisters 
Hospital.  Until  1889  it  consisted  of  only  one  room.  With  the  coming 
of  the  railroad,  however,  the  Northern  Pacific  Beneficial  Association, 
Western  Division,  Relief  Fund  was  organized  in  1882  with  headquar- 
ters in  Missoula.  This  organization,  to  which  all  Montana  employees 
of  the  Northern  Pacific  belonged,  erected  the  Northern  Pacific  Hospital 
in  Missoula  in  1884.  Destroyed  by  fire  in  1892,  the  hospital  was  rebuilt 
in  1893  expanded  in  1901.^^  As  spotted  fever  cases  increased 
toward  the  end  of  the  century,  both  hospitals  cared  for  its  victims. 

Many  of  the  early  physicians  in  the  Bitterroot  had  studied  medicine 
at  respected  schools  in  the  midwest  and  east,  including  the  Saint  Louis 
Medical  School,  Jefferson  Medical  College  in  Philadelphia,  Bellevue 
Hospital  Medical  College  in  New  York,  and  the  University  of  Virginia 
Medical  School. Some  of  these  doctors  made  a  special  effort  to  stay 
abreast  of  the  latest  developments  in  medicine  in  order  to  incorporate 
the  new  techniques  into  their  practices.  Keeping  up  with  new  medical 
discoveries  was  no  easy  task  in  the  1880s,  for  during  this  decade  the 
concept  of  infectious  diseases  was  being  revolutionized.  In  the  mid 
1870s,  Louis  Pasteur,  a  French  chemist,  and  Robert  Koch,  a  German 
physician,  had  demonstrated  that  bacteria  caused  anthrax,  and  their 
findings  launched  a  heady  period  of  searching  for  other  microorganisms 
that  might  be  the  cause  of  dread  epidemics.  During  the  1880s  bacteria 
were  identified  as  the  culprits  in  typhoid  fever,  leprosy,  tuberculosis, 
diphtheria,  tetanus,  pneumonia,  and  bubonic  plague,  among  others. 


A  Blight  on  the  Bitterroot 


17 


Once  bacteria  had  been  demonstrated  as  the  causes  of  particular 
diseases,  scientists  also  sought  to  understand  how  they  were  trans- 
mitted from  one  sick  person  to  another.  By  the  end  of  the  century, 
water,  milk,  insects,  and  human  carriers  had  been  implicated  as  po- 
tential routes  for  the  spread  of  disease/^  Some  diseases,  moreover, 
responded  to  treatment  with  the  blood  serum  of  recovered  victims, 
and  others  were  found  to  be  preventable  by  vaccines  made  from  killed 
or  attenuated  organisms.  It  was,  in  short,  a  period  during  which  dis- 
coveries piled  quickly  on  top  of  one  another  and  the  tree  of  knowledge 
was  ripe  for  picking.  For  young  physicians  and  scientists,  medical 
research  offered  challenging  intellectual  problems,  an  opportunity  to 
contribute  directly  to  the  welfare  of  the  world,  and  even  the  possibility 
of  great  celebrity  for  themselves. 

The  bacteriological  discoveries  also  provided  new  inspiration  to  the 
pubhc  health  or  sanitary  movement  that  had  evolved  in  the  United 
States  primarily  since  the  Civil  War.  This  movement  had  been  divided 
philosophically  between  those  who  attributed  the  cause  of  infectious 
diseases  to  specific  agents  and  others  who  believed  that  poisonous 
vapors,  known  as  miasmas,  rose  from  contaminated  earth  to  bring 
disease.  The  former  group,  called  contagionists,  had  long  advocated 
quarantine  when  disease  was  present,  while  the  latter,  known  as  an- 
ticontagionists,  called  for  strict  sanitary  measures  designed  to  remove 
the  contamination  that  gave  rise  to  miasmas. With  the  advent  of 
bacteriology,  these  two  views  could  be  reconciled,  and  it  appeared  that 
pubhc  health  programs  based  on  scientific  principles  might  indeed  rid 
the  cities  of  the  world  of  recurring  plagues. 

In  the  United  States,  state  and  local  public  health  boards,  which  had 
evolved  since  the  Civil  War  in  urban  eastern  areas,  began  to  multiply 
in  other  areas  of  the  country.  By  1887  the  town  of  Missoula  had 
created  a  board  of  health,  and  in  March  1896  the  Ravalli  County 
Board  of  Health  was  established  in  the  Bitterroot  Valley,  with  Samuel 
W.  Minshall  as  first  chairman. In  1902,  moreover,  the  U.S.  Congress 
also  fostered  the  development  of  public  health  by  providing  for  an 
annual  meeting  of  state  and  territorial  health  officers  with  the  surgeon 
general  of  the  U.S.  Public  Health  and  Marine  Hospital  Service. ^°  It 
was  hoped  that  the  exchange  of  information  at  this  meeting  would 
enhance  the  attack  on  disease  throughout  the  nation. 

On  15  March  1901,  Governor  Joseph  K.  Toole  signed  an  act  passed 
by  the  Legislative  Assembly  creating  a  board  of  health  for  the  state  of 
Montana.  As  in  other  states,  the  Montana  State  Board  of  Health's 
charge  was  broad.  It  was  to  investigate  epidemics;  to  suppress  nuisances 
(that  is,  to  see  that  unpleasant  surroundings  were  cleaned  up);  to 


i8 


Rocky  Mountain  Spotted  Fever 


attempt  to  determine  the  influence  of  locality,  climate,  employments, 
and  habits  on  the  health  of  the  people;  and  to  cooperate  with  local 
boards  of  health.  Unfortunately,  the  budget  allocated  for  this  work 
was  only  two  thousand  dollars  a  year,  its  small  size  another  charac- 
teristic shared  with  many  other  state  boards  of  health.  William  Treacy 
of  Helena  was  elected  president,  and  Albert  F.  Longeway  of  Great 
Falls,  having  just  completed  a  year  as  president  of  the  Montana  Medical 
Association,  was  named  secretary,  the  officer  charged  with  enforcing 
the  board's  poHcies.  Other  members  of  the  board  were  two  physicians, 
James  L.  Belcher  of  Townsend  and  H.  J.  Loebinger  of  Butte;  J.  M. 
Robertson,  a  civil  engineer  from  Bozeman;  and  the  governor  and 
attorney  general  as  ex  officio  members.^ ^ 

It  was  during  this  period,  when  medicine  and  public  health  looked 
forward  optimistically  to  becoming  truly  scientific,  that  the  problem 
of  Rocky  Mountain  spotted  fever  was  first  addressed.  Although  the 
number  of  cases  was  increasing,  paralleling  the  growth  of  the  Bitter- 
root's  population,  only  gradually  was  the  disease  given  the  uniform 
designation  spotted  fever.  Many  early  cases  were  called  black  measles, 
probably  because  measles  was  widely  known  as  an  early  childhood 
affliction,  and  spotted  fever,  with  a  similar  rash,  seemed  to  be  a  ma- 
lignant form  of  it.  The  designations  black  typhus  fever  and  blue  disease 
occasionally  appeared,  and  often  the  disease  was  called  black  fever  or 
simply  fever.^^  Physicians  reporting  on  it  frequently  called  it  typhoid 
pneumonia,  measles,  and  cerebrospinal  meningitis,  because  of  the 
symptoms  it  shared  in  common  with  these  better-known  maladies— 
a  stiff  neck,  headache,  high  fever,  and  rash.^^  Known  to  occur  in  the 
spring,  the  affliction  most  frequently  struck  residents  or  visitors  on  the 
west  side  of  the  Bitterroot  River  and  was  most  often  reported  in  the 
northern  section  of  the  valley,  which  overlapped  Ravalli  and  Missoula 
counties. 

Spotted  fever  was  not  confined  to  the  Bitterroot  Valley  alone,  but 
it  was  known  to  be  considerably  milder  in  other  locations. The  first 
pubhshed  report  on  the  disease,  in  fact,  was  made  in  1896  by  Major 
Marshall  W.  Wood,  a  U.S.  Army  physician  stationed  in  Boise,  Idaho. 
A  native  of  Watertown,  New  York,  who  had  studied  medicine  at  Rush 
Medical  College  in  Chicago,  Wood  mentioned  in  one  of  his  monthly 
reports  the  "prevalence  of  spotted  fever  in  civil  settlements  in  the 
neighborhood  of  his  post."^^  When  the  surgeon  general  of  the  army 
requested  particulars.  Wood  compiled  reports  from  prominent  Idaho 
physicians  because,  although  he  suffered  a  bout  of  the  disease  later, 
he  had  not  at  that  time  seen  any  cases. Their  comments  on  spotted 
fever,  published  in  the  surgeon  general's  annual  report,  revealed  well- 


A  Blight  on  the  Bitter  root 


19 


honed  powers  of  clinical  observation  but  also  reflected  the  endurance 
of  the  older  miasma  theory  of  disease  causation,  especially  when  spec- 
ulative bacteriological  explanations  did  not  correlate  with  epidemio- 
logical findings. 

C.  L.  Sweet,  president  of  the  Idaho  State  Medical  Society,  clearly 
described  the  rash,  the  "breakbone  pains,"  and  the  low  fatality  of 
Idaho  spotted  fever.  He  advised  symptomatic  treatment  for  the  pain 
and  fever,  noting  that  for  mild  cases  he  primarily  prescribed  placebos. 
Acknowledging  that  there  were  "indications  which  seem  to  point  out 
this  pecuhar  affection  as  a  water-borne  disease,"  Sweet  nevertheless 
was  uncomfortable  with  this  theory.  "Frequently  several  cases  occur 
in  a  household,"  he  noted,  while  at  other  times  "only  the  single  case." 
This  epidemiological  picture  militated  against  infection  from  a  com- 
mon water  supply.  Instead,  Sweet  leaned  toward  "other  circumstances" 
that  favored  spotted  fever's  similarity  to  malaria,  a  disease  whose 
transmission  by  mosquitoes  had  not  in  1896  been  demonstrated.  Spot- 
ted fever  was  frequently  seen.  Sweet  noted,  "in  persons  who  have  been 
living  in  the  vicinity  of  newly  broken  ground,  post  holes,  plowed 
ground,  and  in  those  who  have  drunk  seepage  water  from  worked 
soil,  etc."  In  a  similar  analysis,  L.  C.  Bowers  speculated  that  the  true 
cause  of  the  disease  "was  probably  of  a  telluric  character,"  that  is, 
arising  from  the  earth  itself.^^  Ticks  or  tick  bites  were  never  mentioned 
as  possible  factors. 

In  October  1899,  Edward  E.  Maxey,  secretary  of  the  Idaho  State 
Medical  Society,  read  a  paper  about  spotted  fever  before  the  Oregon 
State  Medical  Society.  Published  in  the  Portland,  Oregon,  Medical 
Sentinel^  a  journal  that  had  been  adopted  by  many  western  state  med- 
ical associations  as  an  official  organ,  Maxey's  paper  was  the  first  on 
the  disease  in  a  medical  periodical.  Maxey  observed  that  spotted  fever 
was  "in  all  probability,  caused  by  some  peculiar  organism,  possibly  a 
miasm,"  but  that  "no  specific  cause"  had  "yet  been  discovered."  He 
pointed  out  that  the  disease  invariably  occurred  during  the  spring 
months  and  was  primarily  contracted  "while  residing,  or  sojourning, 
in  or  near  the  foot-hills  of  the  mountains."  Aware  of  the  discoveries 
about  contaminated  water  and  infectious  diseases,  Maxey  noted  that 
while  in  the  foothills  of  the  mountains,  victims  had  no  other  water 
supply  than  that  which  came  from  the  melting  snow.  "In  other  words," 
he  said,  "they  drank  the  snow  water  and  became  sick,  therefore  there 
must  be,  in  my  opinion,  some  specific  cause  for  this  disease,  either  in 
the  soil  over  which  the  water  runs,  or  in  the  snow  itself. "^^ 

Maxey  also  differentiated  between  spotted  fever  and  other  diseases 
with  which  it  had  previously  been  identified.  "After  once  seeing  and 


20 


Rocky  Mountain  Spotted  Fever 


recognizing  spotted  fever,  the  diagnosis  is  easy.  .  .  .  Even  the  laity 
recognize  it  on  sight."  Noting,  however,  that  physicians  had  variously 
called  it "  'dengue  fever,'  cerebro-spinal  meningitis,  typhoid,  rheumatic 
purpura,  typhus  and  measles,"  Maxey  pointed  out  the  seasonal,  ge- 
ographic, or  symptomatic  differences  between  each  of  these  diseases 
and  spotted  fever.  He  reiterated  the  optimistic  prognosis  for  the  disease 
as  know^n  in  Idaho,  and  he  did  not  mention  the  virulent  form  of  spotted 
fever  knov^n  in  the  Bitterroot  Valley. 

Although  there  were  no  published  reports  on  this  disease  from  other 
states  at  this  time,  in  retrospect  it  is  clear  that  spotted  fever  had  been 
recognized  during  the  last  quarter  of  the  nineteenth  century  throughout 
the  northwest  states.  In  Colorado  a  later  survey  noted  that  the  disease, 
which  exacted  about  a  23  percent  mortality,  had  been  known  since 
1 8  8  5 .  In  Oregon  spotted  fever  was  reported  to  be  well  known  to  early 
physicians,  "considered  by  them  a  mysterious  disease  with  considerable 
mortality."  Later  statistics  showed  that  the  death  rate  in  Oregon  was 
"much  less  than  in  Montana"  yet  "somewhat  higher  than  in  Idaho." 
Spotted  fever  was  reported  most  frequently  in  the  central  part  of  eastern 
Oregon,  and,  as  was  the  case  in  Idaho  and  Montana,  it  seemed  to  be 
contracted  in  or  near  the  foothills  of  the  mountains.  No  case  was 
known  west  of  the  Cascade  Mountains."^^ 

In  Wyoming  spotted  fever  apparently  had  been  known  by  the  names 
mountain  typhus,  mountain  sickness,  mountain  fever,  and  similar 
terms.  The  Indians  of  Wyoming  reputedly  knew  of  the  disease  but  did 
not  associate  it  with  any  particular  region  of  the  state.  One  old-time 
prospector  who  had  crossed  the  plains  into  Wyoming  during  the  days 
of  the  "bull  trains"  later  told  a  Wyoming  state  health  officer  that 
spotted  fever  was  commonly  called  trail  typhus  by  emigrants  traveling 
the  Oregon  Trail.  It  had  plagued  them  particularly,  he  stated,  from 
"the  point  where  the  trail  joined  the  Sweetwater  River  about  at  In- 
dependence Rock"  until  they  crossed  the  Green  River.  This  description 
coincided  with  the  central  and  north-central  location  of  the  majority 
of  Wyoming  cases.  Like  the  situation  in  Oregon,  moreover,  mortality 
in  Wyoming  seemed  to  be  about  15—20  percent— higher  than  in  Idaho 
but  lower  than  in  the  Bitterroot  Valley. 

Other  studies  also  concluded  that  spotted  fever  had  been  present 
from  an  early  period  in  Washington,  Nevada,  Utah,  and  CaUfornia.'^^ 
Because  the  mortality  in  these  states  was  relatively  low,  however,  state 
authorities  had  not  initiated  investigations.  The  Montana  State  Board 
of  Health,  on  the  other  hand,  was  confronted  with  the  virulent  spotted 
fever  problem  at  the  first  meeting  it  held  after  being  organized.  The 
issue  was  raised  by  the  Montana  labor  commissioner,  Judson  A.  Per- 


A  Blight  on  the  Bitterroot 


21 


guson,  who  had  been  pressed  to  take  action  on  the  problem  by  Bit- 
terroot lumbermen,  among  whose  ranks  many  victims  of  the  disease 
were  numbered.  Ferguson  had  accordingly  sent  a  questionnaire  to 
Missoula  and  Bitterroot  Valley  physicians  asking  for  as  much  infor- 
mation as  possible  about  spotted  fever.  He  presented  the  replies  at  the 
meeting  of  the  state  board  on  9  May  1901.^"^ 

Although  the  board  was  principally  concerned  at  this  meeting  with 
a  smallpox  epidemic  in  the  state  and  with  establishing  rules  for  licensing 
undertakers,  the  members  listened  to  Ferguson's  report  and  expressed 
willingness  "to  call  a  special  meeting  at  any  time  to  consider  the  matter" 
of  spotted  fever.  Desiring  more  scientific  information,  the  board  au- 
thorized Emil  Starz,  who  was  appointed  state  bacteriologist  later  that 
summer,  to  make  a  bacteriological  investigation  of  the  disease.  Ac- 
companied by  Ferguson,  Starz  visited  the  valley,  took  water  and  soil 
specimens,  and  obtained  "cultures"  from  one  spotted  fever  patient, 
which  he  inoculated  with  negative  results  into  two  rabbits. On  the 
basis  of  his  research,  Starz  hypothesized  that  the  disease  was  really 
"cerebrospinal  meningitis  combined  with  one  or  the  other  of  pneu- 
monia or  typhoid  fever,"  but  he  also  called  for  further  investigation.^^ 

Physicians  and  laymen  who  had  more  direct  experience  with  spotted 
fever  disagreed  sharply  with  Starz.  "While  he  may  be  able  to  peep 
through  a  microscope  and  see  things,"  wrote  one  Missoula  doctor, 
"he  doesn't  know  what  he  is  talking  about  in  this  instance."^"  Although 
no  one  else  had  any  additional  scientific  evidence  to  offer  about  the 
disease,  many  theories  were  advanced.  Melted  snow  water  as  the  source 
of  the  disease  was  the  most  popular  theory  with  Missoula  physicians, 
but  one  Bitterroot  Valley  doctor  asserted  that  spotted  fever  was  gen- 
erated by  miasmas  arising  from  north  winds,  which  blew  over  decaying 
spring  vegetation  in  swampland  on  the  west  side  of  the  valley."*^  A 
layman  from  the  Woodside  area  of  the  valley  scoffed  at  this  thesis. 
Edward  Burrows  noted  that  he  had  lived  for  twelve  to  fourteen  years 
in  the  swampy  area  on  the  west  side  when  it  was  virtually  covered 
with  timber,  yet  no  spotted  fever  had  then  been  known.  "The  land 
was  cleared  in  the  last  six  to  seven  years,"  he  said,  "and  spotted  fever 
began."  Burrows  did  not  suggest  that  the  extensive  lumbering  oper- 
ations in  the  valley  might  be  the  cause  of  the  disease  but  believed 
instead  that  miasmas  from  "dooryard  filth"  were  the  cause. 

There  were  more  than  a  dozen  cases  of  spotted  fever  during  the 
spring  of  1901— one  official  count  noted  fourteen  cases  with  ten 
deaths. When  compared  with  the  number  of  deaths  in  Montana  from 
smallpox,  diphtheria,  and  typhoid,  virulent  spotted  fever  was  not  a 
widespread  menace  to  pubUc  health.  Like  the  infrequent  visitations  of 


22 


Rocky  Mountain  Spotted  Fever 


cholera  and  yellow  fever,  however,  the  few  spring  cases  of  spotted 
fever  each  year  struck  fear  in  valley  inhabitants.  The  dramatic  symp- 
toms of  the  disease— the  blue-black  rash,  high  fever,  and  delirium  — 
and  the  high  mortahty  rate,  especially  among  the  healthy  young  adults 
who  were  among  its  most  frequent  victims,  produced  anxiety  about 
an  early  and  horrible  death.  Furthermore,  this  dread  disease  seemed 
a  particularly  cruel  blight  on  the  future  development  of  one  of  the 
most  beautiful  valleys  in  the  western  United  States.  Proposals  for  at- 
tracting new  residents  who  wished  to  grow  apples  on  irrigated  farms 
were  already  being  discussed,  and  the  west  side  of  the  valley  was  prime 
land  for  this  purpose.  If  a  deadly  infection  lurked  in  the  west  side 
canyons,  however,  prospective  land  buyers  would  be  understandably 
reluctant  to  place  themselves  in  jeopardy.  Economic  aspirations  of 
valley  residents  thus  fueled  a  desire  to  "do  something"  about  spotted 
fever.  Decisions  made  by  the  Montana  State  Board  of  Health  in  the 
spring  of  1902  addressed  this  demand  and,  in  so  doing,  launched 
twentieth-century  research  efforts  to  understand,  prevent,  and  treat 
this  mysterious  disease. 


Chapter  Three 


The  Beginning  of  Scientific 
Investigations 

The  great  tragedy  of  Science— the  staying  of  a  beautiful  hypothesis  by  an 
ugly  fact. 

Thomas  Huxley,  Collected  Essays 


In  1902  scientific  experts  began  a  decades-long  search  to  elucidate 
the  etiolog)',  prevention,  and  treatment  of  the  mysterious  spotted  fever 
of  the  Rocky  Mountains.  During  the  first  nvo  seasons  of  this  work, 
in  1902  and  1903,  it  seemed  that  the  etiolog)^  of  spotted  fever  might 
quickly  be  explained,  for  the  evidence  indicated  that  the  disease  was 
caused  by  a  protozoan  organism  transmitted  by  the  Rocky  Mountain 
wood  tick.  In  1904,  however,  this  theory  was  called  into  question  by 
other  scientific  specialists.  For  the  inhabitants  of  the  Bitterroot  con- 
tinually at  risk  of  contracting  the  disease,  each  new  finding  seemed 
only  to  make  it  clear  that  their  strange  disease  was  more  complex  than 
anyone  had  previously  envisioned. 

Placing  spotted  fever  investigations  on  a  scientific  basis  began  at  the 
February  1902  meeting  of  the  Montana  State  Board  of  Health.  Since 
cases  of  the  malady  rarely  appeared  before  mid  March,  the  board 
could  do  little  at  the  time,  but  it  agreed  unanimously  to  pursue  the 
problem  "as  soon  as  the  occasion  arose."  In  early  April  spotted  fever 
struck  near  Florence,  a  well-known  infected  area.  By  the  end  of  the 
month  there  had  been  five  cases  in  the  valley,  three  of  which  were 
from  the  Hamilton  area,  south  of  the  Florence  — Lo  Lo  spotted  fever 
district,  and  concern  was  voiced  that  the  disease  was  spreading.^ 

The  RavalH  Count)'  Board  of  Health  met  on  28  April  to  discuss  the 
problem.  Local  physicians  affirmed  that  this  disease  was  neither  typhus 
nor  cerebrospinal  meningitis,  the  two  "spotted  fevers"  discussed  in 
medical  textbooks.  They  called  for  the  state  board  of  health  to  employ 
an  expert  pathologist  to  study  the  problem  scientifically.^  The  Montana 
state  labor  commissioner,  Judson  A.  Ferguson,  who  had  initially 


^3 


2-4 


Rocky  Mountain  Spotted  Fever 


brought  the  spotted  fever  question  to  the  attention  of  the  state  board 
in  1 90 1,  also  pressed  the  board  for  "decisive  measures"  to  suppress 
the  disease  that  attacked  many  of  the  lumbermen  who  were  his  con- 
stituents.^ 

Responding  to  this  outcry,  members  of  the  state  board  of  health 
visited  the  valley  in  early  May.  The  board's  secretary,  Albert  F.  Longe- 
way,  brought  along  Earle  Strain,  a  medical  colleague  from  Great  Falls 
who  had  studied  bacteriology  in  Europe.  When  Strain  noticed  a  tick 
in  the  hair  around  the  genitals  of  a  spotted  fever  victim,  he  reportedly 
recalled  a  lecture  given  by  John  Guiteras  at  the  University  of  Penn- 
sylvania on  mosquitoes  as  the  vector  of  yellow  fever.  He  suggested  to 
Longeway  that  the  tick  might  have  a  similar  connection  with  spotted 
fever.^ 

On  the  whole,  however,  Longeway  was  disappointed  that  little  was 
accompUshed  by  this  visit  "aside  from  obtaining  information  about 
past  illnesses  and  specimens  of  water  and  soil  for  laboratory  study," 
but  he  decided  that  the  services  of  a  scientific  expert  were  indeed 
needed.  He  wired  Governor  Joseph  K.  Toole,  who  was  in  Washington, 
D.C.,  attending  a  family  funeral,  for  permission  to  act.  Toole's  reply 
instructed  Longeway  "to  employ  the  best  skill  that  money  could  secure 
and  carry  to  conclusion  a  most  thorough  investigation."^ 

Armed  with  the  governor's  approval,  Longeway  consulted  H.  M. 
Bracken,  secretary  of  the  Minnesota  State  Board  of  Health,  who,  along 
with  Frank  F.  Wesbrook,  director  of  that  board's  bacteriological  lab- 
oratory, suggested  two  young  pathologists  on  their  staff  as  potential 
investigators.  The  two,  whose  services  Longeway  promptly  engaged, 
were  Louis  B.  Wilson,  an  assistant  bacteriologist  with  the  state  board 
and  senior  demonstrator  in  pathology  at  the  University  of  Minnesota, 
and  WiUiam  M.  Chowning,  a  junior  demonstrator  in  pathology  at  the 
university  and  staff  pathologist  to  Saint  Mary's  Hospital  and  the  Min- 
neapolis City  Hospital.  Born  in  1866,  Wilson  had  studied  with  Wes- 
brook as  a  medical  student  at  the  University  of  Minnesota,  after  which 
he  spent  a  period  at  Harvard  with  Frank  Burr  Mallory,  who  developed 
many  of  the  tissue  stains  widely  used  in  histologic  pathology.^  Wilson's 
resulting  laboratory  expertise  earned  him  second  author  status  in  1900 
on  a  distinguished  Wesbrook  paper  concerning  the  varieties  of  the 
diphtheria  bacillus.^  Wilson's  associate,  twenty-nine-year-old  William 
M.  Chowning,  had  taken  undergraduate  degrees  at  Knox  College  and 
Johns  Hopkins  University  and  had  just  completed  his  M.D.  in  1901 
at  the  University  of  Minnesota  Medical  School.^  The  Montana  State 
Board  of  Health  hoped  that  Wilson  and  Chowning,  with  their  expertise 


The  Beginning  of  Scientific  Investigations 


2-5 


In  1902,  Louis  B.  Wilson  (left)  and  William  M.  Chowning,  young  patholo- 
gists from  the  University  of  Minnesota,  launched  scientific  investigations 
into  Rocky  Mountain  spotted  fever.  Wilson  later  pursued  a  distinguished 
career  at  the  Mayo  Clinic  in  Rochester,  Minnesota.  Chowning  returned  to 
the  private  practice  of  medicine.  (Courtesy  of  the  Rocky  Mountain  Labora- 
tories, NIAID.) 

in  pathology  and  bacteriology,  would  be  able  to  shed  light  on  the 
Bitterroot's  strange  blight. 

Because  the  spotted  fever  season  v^as  so  short  each  year,  the  two 
pathologists  began  v^ork  almost  immediately.  Arriving  in  Missoula  on 
16  May,  Wilson  wa.s  joined  by  Chowning  on  26  May.  With  apparatus 
and  media  brought  from  Minnesota,  they  established  a  laboratory  in 
a  Northern  Pacific  Hospital  room  made  available  for  the  work.  The 
railroad  company  was  eager  to  assist  in  the  spotted  fever  investigations, 
because  the  expansion  of  its  rail  lines  into  Idaho  was  jeopardized  by 
the  disease,  as  was  its  supply  of  lumber  for  ties  from  the  Bitterroot. 
The  physicians  who  administered  the  hospital,  J.  J.  Buckley  and  E.  W. 
Spottswood,  cooperated  fully  with  the  visiting  investigators,  loaning 
the  two  men  additional  equipment.  The  arrival  of  Wilson  and  Chown- 
ing marked  the  beginning  of  scientific  research  into  Rocky  Mountain 
spotted  fever.^ 


26 


Rocky  Mountain  Spotted  Fever 


The  investigation  was  broad:  data  were  gathered  from  epidemio- 
logical, clinical,  pathological,  and  laboratory  studies.  Within  the  first 
ten  days,  the  two  pathologists  conducted  three  autopsies;  subsequently 
they  conducted  five  more.  Victims  of  spotted  fever,  they  observed, 
showed  an  enlarged  spleen  and  small  hemorrhages  in  the  kidneys  and 
at  the  base  of  the  left  ventricle  of  the  heart.  Most  other  organ  systems 
appeared  normal.  Employing  staining  techniques  by  which  the  minute 
changes  in  tissues  could  be  seen  under  the  microscope,  Wilson  and 
Chowning  found  that  the  capillaries  of  the  skin  were  distended  and 
that  many  blood  cells  had  escaped  into  the  surrounding  tissue.  This, 
of  course,  explained  the  presence  of  the  "spots. 

To  gather  epidemiological  evidence,  Wilson  wrote  each  physician 
in  the  Bitterroot  and  Missoula,  asking  for  detailed  case  histories  on 
spotted  fever  patients.  He  enclosed  a  blueprint  map  of  the  valley  on 
which  the  suspected  point  at  which  victims  contracted  the  disease  was 
to  be  marked  with  "a  pen  dipped  in  a  strong  solution  of  common 
baking  soda."  The  response  was  satisfying— all  but  one  physician  re- 
sponded, providing  information  from  their  records  on  114  cases. 

Data  from  the  blueprint  maps  were  combined  on  a  master  map  that 
showed  definitively  the  sharp  localization  of  spotted  fever  on  the  west- 
ern side  of  the  Bitterroot  Valley.  Two  other  foci  were  also  identified 
outside  the  valley  in  western  Montana. In  the  Bitterroot,  furthermore, 
the  infected  district  did  not  include  the  entire  west  side  of  the  valley. 
A  later  observer  noted: 

The  boundary  of  the  endemic  area  is  not  formed  by  the  river  but  by  the  margin 
of  the  "bench"  or  foothills.  People  living  in  the  river  bottom,  even  on  the  west 
side,  feel  secure.  .  .  .  Exposure  or  residence  on  the  "bench"  might  for  some 
reason  be  more  dangerous  than  in  other  near  places  because  of  the  difference 
in  the  development.  The  east  side  of  the  valley  is  cleared  thoroughly,  highly 
cultivated,  v^ell  settled  and  in  thrift  and  prosperity  resembles  a  fat  Pennsylvania 
or  Ohio  Valley.  The  west  side,  especially  the  "bench,"  is  not  nearly  so  advanced. 
Much  of  it  is  not  cleared  at  all,  very  little  is  well  cultivated.  The  houses  as  a 
rule,  are  poor  and  there  is  a  difference  of  many  years  in  the  advancement  of 
the  two  sides. 

Other  information  from  Wilson  and  Chowning's  epidemiological 
study  revealed  that  the  earliest  recorded  case  began  on  17  March  and 
the  latest  about  20  July,  with  most  cases  occurring  between  15  May 
and  15  June.  An  analysis  of  the  sex  and  age  of  victims  revealed  that 
although  the  disease  had  occurred  in  both  sexes  and  in  all  age  groups, 
the  highest  incidence  was  in  males  between  20  and  40  years  old— a 
total  of  41  cases  in  this  group  — and  in  females  between  10  and  20 
years  old  or  between  30  and  40— there  were  11  cases  in  each  of  these 


Highlighted  version  of  the  epidemiological  map  prepared  in  1902  by  Louis  B. 
Wilson  and  William  M.  Chowning  during  their  study  of  spotted  fever  in  the  Bit- 
terroot  Valley.  The  horizontal  line  near  the  top  marks  the  political  division  be- 
tween Missoula  and  Ravalli  counties.  The  dots  representing  cases  clearly  shov^ 
the  concentration  of  the  disease  on  the  benchlands  and  in  the  canyons  west  of  the 
Bitterroot  River.  (From  Louis  B.  Wilson  and  William  M.  Chov^ning,  "Studies  in 
Pyroplasmosis  Hominis:  ['Spotted  Fever'  or  'Tick  Fever'  of  the  Rocky  Moun- 
tains],"/owr«<3/  of  Infectious  Diseases  i  [1904]:  31-57.) 


28 


Rocky  Mountain  Spotted  Fever 


TABLE  I. 

Wilson  and  Chowning's  Record 

of  Spotted  Fever  Cases 

by  Age  and  Sex 

of  Patients 

Males 

Females 

Total 

Age 

Cases 

Deaths 

Cases 

Deaths 

Cases 

Under  5 

8 

4 

5 

5 

13 

5-10 

6 

5 

7 

4 

13 

10-20 

8 

5 

11 

5 

19 

20-30 

17 

13 

7 

3 

24 

30^0 

OA 

1  Q 

1 1 

7 

J  J 

40-50 

8 

6 

2 

1 

10 

50-60 

3 

2 

2 

1 

5 

60-80 

4 

4 

2 

2 

6 

Not  stated 

1 

1 

0 

0 

1 

TOTAL 

79 

59 

47 

28 

126 

SOURCE:  This  table  is  adapted  from  Louis  B.  Wilson  and  William  M.  Chowning,  "Studies  in 
Pyroplasmosis  Hominis"  ('Spotted  Fever'  or  'Tick  Fever'  of  the  Rocky  Mountains),"  Journal  of 
Infectious  Diseases  1  (1904):  36.  It  includes  information  on  cases  studied  in  1903  in  addition  to 
the  114  cases  on  which  records  were  compiled  in  1902. 


two  age  groups  (see  Table  i).  Wilson  and  Chowning  attributed  the 
higher  infection  rate  in  these  groups  to  the  "increased  exposure  to 
infection  through  their  occupation  or  pleasure  taking  them  outdoors 
in  the  foothills  and  mountains  in  the  spring  of  the  year."  From  clinical 
histories  of  the  cases,  moreover,  Wilson  and  Chowning  noted  that  the 
"general  health  of  the  patient"  had  "little  part  in  determining  suscep- 
tibility to  the  disease."  In  general,  victims  of  spotted  fever  were  healthy 
before  the  disease  struck  them  down.^"^ 

Wilson  and  Chowning  determined  that  between  1895  ^^'^  1902, 
the  years  during  which  spotted  fever  had  become  a  fearsome  presence 
in  the  valley,  there  had  been  88  cases  with  64  deaths,  producing  an 
average  mortality  of  72.7  percent.  Their  records  correlated  closely 
with  newspaper  reports  during  these  same  years,  the  newspapers  re- 
cording 92  probable  cases  with  64  deaths,  a  mortality  rate  of  69.56 
percent  (see  Table  2).^^  As  a  part  of  their  examination  of  the  "to- 
pography, meteorology  and  water  and  food  supply,"  moreover,  they 
found  that  "in  no  instance  have  two  or  more  persons  with  the  same 
food  or  water  supply  been  simultaneously  stricken  with  the  disease." 
This  finding  cast  doubt  on  melted  snow  water  as  the  source  of  the 
infection.  Neither  was  spotted  fever  contagious.  "There  is  not  even  a 
suspicion,"  they  wrote,  that  the  disease  had  ever  been  "transferred 
directly  from  one  human  being  to  another,  except  in  one  instance,  in 


The  Beginning  of  Scientific  Investigations 


29 


TABLE  2.  Cases  and  Deaths  from  Rocky  Mountain  Spotted  Fever, 


Year 

Wilson  and  Chowning 

Newspapers 

Cases 

Deaths 

Cases 

Deaths 

1895 

3 

3 

6 

6 

1896 

6 

6 

9 

7 

1987 

6 

5 

12 

9 

1898 

3 

2 

11 

8 

1899 

23 

14 

10 

3 

1900 

12 

9 

14 

11 

1901 

14 

10 

17 

10 

1902 

21 

15 

13 

10 

TOTAL  88 

64 

92 

64 

Average  mortality 

72.73% 

69.57% 

SOURCE:  Louis  B.  Wilson  and  William  M.  Chowning,  Report,  Montana  State  Board  of  Health, 
First  Biennial  Report,  1901-1902,  32-41;  idem,  "Studies  in  Pyroplasmosis  Hominis,"  33;  local 
newspapers  as  cited  in  Robert  N.  Philip,  "A  Journalistic  View  of  Western  Montana,  1870-1910: 
Some  Newspaper  Items  Relevant  to  the  Development  of  the  Bitter  Root  Valley  and  the  Occurrence 
of  Rocky  Mountain  Spotted  Fever,"  manuscript,  1984,  passim. 


which  an  infant  born  while  the  mother  was  suffering  from  the  disease" 
also  developed  spotted  fever.  What  they  found  instead— in  every  case 
they  personally  examined— were  "small  wounds  of  the  skin,  said  to 
have  been  made  by  the  bites  of  ticks."  Working  from  this  epidemio- 
logical picture,  Wilson  and  Chowning  began  a  series  of  laboratory 
experiments  to  elucidate  the  microscopic  etiology  of  spotted  fever. 

The  intellectual  milieu  in  which  the  two  pathologists  launched  their 
laboratory  studies  was  strongly  influenced  by  recent  discoveries  relating 
to  microorganisms  and  their  potential  vectors.  Epidemiological  data 
from  earlier  periods,  for  example,  such  as  those  gathered  in  the  1848- 
49  London  cholera  epidemic  by  John  Snow,  had  suggested  that  con- 
taminated water  might  be  one  vector  by  which  bacteria  were  trans- 
mitted. This  theory  was  confirmed  in  1884  when  Robert  Koch  dis- 
covered the  comma-shaped  bacillus  of  cholera,  and  subsequently  water 
was  suspect  whenever  a  new  disease  was  investigated.  That  the  lay 
population  of  the  Bitterroot  was  familiar  with  the  concept  of  water- 
borne  disease  is  evident  in  the  popularity  of  the  theory  that  held  melted 
snow  water  to  be  the  source  of  spotted  fever. 

Another  recently  discovered  route  by  which  bacterial  diseases  were 
spread  was  insects,  such  as  flies  and  mosquitoes,  and  other  arthropods 
such  as  ticks  and  mites.  Transmission  of  bacterial  diseases  by  insects 


30 


Rocky  Mountain  Spotted  Fever 


The  Rocky  Mountain  wood  tick,  male  and  female  Dermacentor  andersoni, 
the  first  tick  identified  as  a  vector  of  Rocky  Mountain  spotted  fever. 
(Courtesy  of  the  Rocky  Mountain  Laboratories,  NIAID.) 


was  believed  to  be  a  mechanical  process:  the  insect  accidentally  picked 
up  bacteria  on  its  wrings,  feet,  or  mouth  parts  and  carried  them  to  food 
or  other  items  contacted  by  a  human  or  animal  host.  The  Spanish- 
American  War  of  1898  had  produced  a  convincing  and  well-publicized 
indictment  of  one  insect,  the  house  fly,  in  connection  with  the  me- 
chanical transmission  of  typhoid  fever.  An  official  investigation  of  the 
typhoid  epidemic  in  U.S.  camps  documented  the  proximity  of  open 
latrines  to  cooking  tents,  noted  the  swarms  of  flies  with  access  to  both, 
and  concluded  that  authorities  concentrating  on  the  purity  of  the  water 
supplies  had  neglected  to  address  the  threat  of  transmission  of  typhoid 
by  flies.i" 

A  second  line  of  inquiry  about  arthropods  and  disease  had  grown 
out  of  research  in  helminthology,  the  study  of  parasitic  worms. In 
1878,  Patrick  Manson,  a  British  medical  officer  studying  the  life  cycle 
of  Filaria  bancrofti,  the  worm  that  causes  the  tropical  disease  filariasis, 
discovered  that  a  portion  of  the  worm's  life  cycle  was  spent  in  the 
body  of  a  mosquito. Manson's  research  inspired  Ronald  Ross,  an- 
other British  medical  officer,  to  complete  experiments  that  in  1898 
demonstrated  the  presence  of  the  malaria  parasite,  a  protozoan  rather 
than  bacterial  organism,  in  the  mid  guts  of  Anopheles  mosquitoes. 
Although  credit  for  this  discovery  was  shared  with  Italian  investigator 
Giovanni  Battista  Grassi  and  his  collaborators,  Ross  reaped  high  hon- 
ors. Fellowship  in  the  Royal  Society,  a  Nobel  prize,  and  knighthood 


The  Beginning  of  Scientific  Investigations 


31 


followed  the  realization  that  mosquito  control  measures  might  rid  the 
world  of  the  scourge  of  malaria  and  improve  the  habitability  of  Eu- 
rope's tropical  colonies. ^° 

Five  years  before  Ross's  achievement,  Theobald  Smith  and  Fred 
Lucius  Kilbourne,  a  physician  and  a  veterinarian  working  in  the  Bureau 
of  Animal  Industry  of  the  U.S.  Department  of  Agriculture,  published 
the  results  of  their  experiments  on  Texas  cattle  fever.  They  proved 
conclusively  that  this  disease,  which  resulted  in  a  significant  economic 
loss  to  owners,  was  caused  by  the  presence  in  the  blood  of  a  protozoan 
organism  transmitted  to  the  cattle  by  the  bite  of  an  infected  tick. 
Moreover,  they  demonstrated  that  dipping  cattle  to  kill  ticks  would 
effectively  prevent  the  disease. 

The  disease  organisms  of  filariasis,  malaria,  and  Texas  cattle  fever 
spent  some  portion  of  their  life  cycles  developing  in  the  body  of  an 
intermediate  arthropod  host,  which  passed  them  on  to  humans  or 
animals  through  direct  inoculation  by  biting.  This  developmental  phe- 
nomenon, not  shared  by  bacteria,  defined  initially  the  concept  of  bi- 
ological transmission  of  disease  by  arthropods.  Pathogenic  helminths 
and  protozoa,  moreover,  could  not  be  cultured  as  bacteria  were.  The 
discovery  that  microorganisms  other  than  bacteria  could  be  sources 
of  disease  offered  an  explanation  for  a  major  problem  besetting  bac- 
teriologists. Robert  Koch  had  included  as  one  of  his  postulates  for 
demonstrating  bacterial  etiology  of  disease  the  isolation  and  culture 
on  an  artificial  medium  of  the  suspected  organism. Attempts  to  cul- 
ture the  organisms  of  yellow  fever,  rabies,  and  several  other  diseases 
had  proven  fruitless,  but  after  the  discoveries  of  Manson,  Ross,  and 
Smith  and  Kilbourne,  many  researchers  suspected  that  the  elusive  or- 
ganisms of  a  number  of  dread  diseases  were  pathogenic  protozoa  or 
helminths.  When  the  U.S.  Yellow  Fever  Commission  in  Cuba  dem- 
onstrated that  Yellow  Jack  was  a  mosquito-borne  disease,  this  sus- 
picion became  a  working  hypothesis. 

At  the  time  these  discoveries  were  made,  moreover,  the  concept  of 
the  virus  as  a  distinct  pathologic  entity  did  not  exist.  The  term  virus 
was  used  only  in  the  general  sense,  like  the  word  germ,  to  mean 
"infectious  agent."  As  such,  it  was  appHed  to  bacterial,  protozoan, 
and  unknown  pathogens.  A  few  physical  scientists  argued  that  the  so- 
called  filterable  viruses  might  be  nonliving  substances,  but  most  medical 
and  bacteriological  researchers,  who  were  advocates  of  the  germ  the- 
ory, supported  the  idea  that  ultramicroscopic  agents  were  tiny,  living 
microbes. 

The  intellectual  concepts  that  emerged  from  these  findings  linked 
bacterial  diseases  to  mechanical  transmission  of  diseases  by  arthropod 


32 


Rocky  Mountain  Spotted  Fever 


vectors  and  protozoan  diseases  to  biological  transmission.  Most  re- 
searchers never  concluded  that  these  relationships  were  rigid,  but  in 
the  face  of  no  conflicting  evidence,  they  often  came  to  assume  them 
as  truth.  In  1899,  for  example,  George  H.  F.  Nuttall,  founder  of  the 
journal  Parasitology^  published  the  first  exhaustive  study  of  arthropod 
vectors.  Simply  by  focusing  on  know^n  information  and  adopting  a 
skeptical  attitude  about  alternative  hypotheses,  Nuttall  reinforced  such 
assumptions.  In  his  section  on  ticks,  he  discounted  the  likelihood  that 
they  carried  any  sort  of  bacterial  infection  biologically,  but  he  discussed 
at  length  tick  transmission  of  protozoan  diseases,  especially  Texas  cattle 
fever.^^ 

This  model  of  hov^  nature  operated  was  powerful  in  suggesting  what 
sort  of  disease  to  suspect  given  a  known  insect  vector.  House  flies,  for 
example,  were  known  to  carry  bacterial  diseases,  but  ticks  and  mos- 
quitoes should  be  suspected  of  carrying  protozoan  diseases.  Con- 
versely, if  a  disease  were  of  known  bacterial  origin,  accidental  trans- 
mission by  an  insect  should  be  investigated,  while  if  a  protozoan  or 
helminth  had  been  identified,  an  arthropod  that  transmitted  the  disease 
biologically  might  be  the  likely  culprit.  During  the  first  three  decades 
of  the  twentieth  century,  the  elegant  logic  of  these  concepts  exerted  a 
powerful  influence  on  researchers  in  infectious  diseases,  including  Wil- 
son and  Chowning  and  subsequent  investigators  of  Rocky  Mountain 
spotted  fever. 

All  of  the  patients  Wilson  and  Chowning  examined  had  been  bitten 
by  wood  ticks  from  two  to  eight  days  before  the  onset  of  the  disease, 
hence  they  suspected  the  tick  as  the  likely  vector.  Local  citizens,  more- 
over, may  also  have  suggested  the  possibility  of  tick  transmission,  for 
ticks  had  occasionally  been  associated  with  "blood  poisoning."^^  By 
analogy  with  known  diseases  transmitted  by  ticks,  Wilson  and  Chown- 
ing doubtless  theorized  that  a  protozoan  organism  might  be  the  in- 
fectious agent.  To  rule  out  possible  bacterial  causation,  however,  they 
examined  fresh  blood  from  patients  and  also  attempted  to  culture 
bacteria  from  blood  in  a  variety  of  media.  All  of  these  studies  were 
negative,  so  they  concluded  that  the  disease  was  not  caused  by  a 
bacterium.  In  the  blood  of  eight  patients,  however,  they  believed  that 
they  saw  "ovoidal  bodies"  that  exhibited  "amoeboid  movements." 
Their  studies  convinced  them  that  these  bodies  were  a  hitherto  un- 
described  "hematozoan,"  a  protozoan  parasite  that  lived  all  or  a  part 
of  its  life  cycle  in  the  circulating  blood  of  its  host.^^  They  announced 
their  findings  to  the  local  press  June  7. 


The  Beginning  of  Scientific  Investigations 


33 


We  find  the  disease  to  be  a  disease  of  the  blood.  It  is  due  to  a  parasite  which 
infests  the  red  blood  cells.  This  parasite  .  .  .  resembles  the  parasite  which 
causes  malaria.  The  parasite  apparently  does  not  gain  access  to  the  body  by 
way  of  the  nose  or  mouth;  that  is,  it  is  not  carried  by  the  air,  drinking  water 
or  food,  but  is  injected  into  the  blood  by  some  biting  insect  or  animal.  .  .  . 
All  the  facts  point  to  some  kind  of  a  tick  as  carrying  the  disease  to  man  by 
its  bite.  All  of  the  above  facts  are  circumstantial  though  not  positive  evidence 
that  the  parasite  of  spotted  fever  is  conveyed  to  man  through  the  bite  of  some 
small  slowly  moving  animal  or  insect  which  is  found  early  in  the  spring  and 
disappears  about  July  and  only  a  few  individuals  of  which  are  infested  with 
the  parasite.  The  tick  answers  to  this  description,  though  much  work  may  yet 
be  needed  to  determine  its  exact  relationship  to  conveyance  of  the  disease.^* 

Wilson  and  Chowning  identified  the  hematozoan  organism  as  a 
Pyroplasma,  other  species  of  which  were  known  to  cause  Texas  cattle 
fever  and  similar  blood  diseases  in  horses  and  dogs.  They  proposed 
that  the  organism  be  named  Pyroplasma  hominis,  or  "the  pyroplasma 
of  humans."  Shortly  after  they  published  their  findings  regarding  this 
organism,  it  should  be  noted,  their  spelling  was  corrected  to  Firoplasma 
to  conform  with  accepted  zoological  nomenclature.  They  described 
three  stages  in  which  they  found  the  organism,  which  they  said  varied 
in  size  from  one  to  three  microns  in  thickness  and  from  two  to  five 
microns  in  length. This  piroplasma,  they  stated,  resembled  "in  its 
smaller  form  very  markedly  the  Pyrosoma  bigeminum  of  Texas  fever, 
yet  [it]  differs  from  that  organism  in  being  larger,  and  in  its  larger 
forms  exhibiting  active  ameboid  movements  with  the  projection  of 
pseudo-podia.  The  absence  of  pigment  from  the  organism  of  'spotted 
fever'  would  apparently  separate  it  from  the  malarial  group  and  place 
it  with  that  of  Texas  fever."^° 

Although  they  admitted  that  this  newly  described  organism  was  not 
always  easy  to  find  in  blood,  many  protozoan  organisms  were  similarly 
difficult  to  locate.  What  doubtless  convinced  them  that  the  elusive 
organism  was  indeed  the  cause  of  spotted  fever  were  the  other  elements 
in  the  paradigm  under  which  they  operated.  The  disease  was  most 
prevalent  during  the  spring  of  the  year,  the  time  when  ticks  were 
plentiful.  All  of  the  cases  of  the  disease  they  observed  had  shown 
evidence  of  tick  bite  before  the  symptoms  appeared.  The  local  ground 
squirrel,  Citellus  columbianus,  moreover,  existed  in  large  numbers  in 
the  valley,  and  it  was  presumed  that  this  mammal  served  as  the  natural 
reservoir  of  the  disease,  from  which  the  infected  ticks  contracted  it.  It 
was  known,  moreover,  and  pointed  out  by  a  later  observer,  that  the 
ground  squirrel  would  not  cross  water  except  under  extraordinary 
circumstances.  "This  being  true,  it  would  give  the  necessary  expla- 


34  Rocky  Mountain  Spotted  Fever 

nation  why  the  disease  was  confined"  to  the  western  side  of  the  valley 

Regarding  the  relationship  between  the  parasite  and  the  tick,  Wilson 
and  Chowning  noted:  "All  hematozoa  of  warm-blooded  animals,  of 
which  the  life  cycle  is  now  known,  pass  at  least  one  phase  of  their 
development  within  the  body  of  some  host  (usually  an  insect  or  arach- 
nid) other  than  the  one  whose  blood  cells  they  invade.  This  is  probably 
also  true  of  the  hematozoan  of  'spotted  fever.'  "  They  also  noted  that 
in  both  malaria  and  Texas  fever,  only  one  species  of  mosquito  or  tick 
carried  the  organism  and  not  all  members  of  the  species  were  infected. 
This  comment  was  offered  to  explain  the  low  incidence  of  infection 
in  the  Bitterroot,  because,  as  the  local  people  noted,  it  was  impossible 
to  escape  being  bitten  during  "tick  season"  each  spring.^^ 

The  P/ro/7/<3sm^2-tick-ground  squirrel  theory  of  spotted  fever  con- 
tained all  the  elements  of  an  elegant  solution  to  a  scientific  mystery, 
and  it  was,  as  a  later  writer  noted,  "in  the  Hne  of  some  of  the  most 
fashionable  thought"  of  the  time.^^  It  conformed  to  prevailing  beliefs 
about  the  relationship  between  protozoan  organisms  and  biological 
transmission  of  disease;  it  identified  a  common  mammal  as  probable 
host  in  nature;  and  it  squared  with  the  epidemiological  data  on  the 
disease.  Furthermore,  this  theory  also  gained  currency  from  immediate 
experience.  On  14  June,  a  week  after  Wilson  and  Chowning  had 
announced  their  findings,  Dan  McDonald,  a  lumberman  who  worked 
on  the  west  side  of  the  valley  near  Victor,  discovered  a  tick  attached 
to  his  body.  As  he  took  it  off,  he  remarked,  "Now  we  shall  see  whether 
this  gives  me  the  spotted  fever  or  not."  Fourteen  days  later  he  died  of 
the  disease. 

While  Wilson  and  Chowning  were  conducting  their  research  in  the 
Bitterroot,  Montana  Congressman  Caldwell  Edwards  had  been  dis- 
cussing the  spotted  fever  situation  with  Walter  Wyman,  surgeon  general 
of  the  U.S.  Public  Health  and  Marine  Hospital  Service.  In  1901  this 
Service,  founded  to  serve  the  medical  needs  of  merchant  seamen,  re- 
ceived congressional  authorization  to  investigate  "infectious  and  con- 
tagious diseases  and  matters  pertaining  to  the  public  health."  Edwards 
or  others  had  indicated  to  Wyman  that  spotted  fever  was  "highly 
communicable  and,  therefore,  a  matter  of  importance  to  the  pubhc 
health  of  the  country."  The  presumed  contagious  nature  of  the  disease 
placed  it  within  the  Service's  purview,  hence  on  23  June,  Wyman 
telegraphed  one  of  his  commissioned  officers,  Surgeon  Julius  O.  Cobb, 
to  proceed  to  Montana  to  investigate  the  disease. 

The  thirty-nine-year  old  Cobb,  a  fourteen-year  veteran  of  the  Service 
from  South  Carolina,  had  considerable  experience  investigating  out- 
breaks of  disease.  Having  contracted  yellow  fever  in  1897,  moreover, 


The  Beginning  of  Scientific  Investigations 


35 


he  doubtless  had  a  keen  appreciation  of  the  new  information  regarding 
the  biological  transmission  of  disease  by  arthropods.  Cobb  reviewed 
the  findings  of  Wilson  and  Chowning  and  agreed  with  their  conclu- 
sions. In  his  report  to  Surgeon  General  Wyman,  Cobb  stated  that  he 
omitted  "many  interesting  facts"  because  they  had  been  published 
already  by  Wilson  and  Chowning  as  a  preliminary  note  in  the  Journal 
of  the  American  Medical  Association.  He  summarized  the  findings  of 
the  two  Minnesota  pathologists  and,  from  his  own  investigation,  was 
satisfied  that  they  had  indeed  found  a  hematozoon  in  the  blood  of 
spotted  fever  victims  that  was  probably  transmitted  to  humans  by  the 
wood  tick  from  a  natural  reservoir  in  the  local  ground  squirrel.  Assured 
that  the  investigations  were  on  the  right  track,  Cobb  noted  that  the 
original  fear  of  contagion  was  "altogether  groundless,"  and  com- 
mented that  "the  alarm  caused  by  newspaper  reports"  was  "unjusti- 
fiable."^^ 

At  the  end  of  the  1902  spotted  fever  season,  Wilson  and  Chowning 
submitted  to  the  Montana  State  Board  of  Health  a  bill  for  $1,466, 
which,  in  light  of  the  board's  annual  budget  of  $2,000,  starkly  revealed 
the  high  cost  of  scientific  research.  For  this  sum,  the  investigators  had 
produced  a  logical  but  unproven  theory  regarding  the  cause  of  spotted 
fever.  They  had  not,  however,  developed  any  method  to  prevent  or  to 
cure  the  malady.  At  the  meeting  of  the  state  board  during  which  the 
expenses  were  allowed,  there  was  considerable  discussion  about  the 
investigation  of  spotted  fever  and  about  the  state's  authority  for  un- 
dertaking it.  The  board  concluded  that  no  more  state  money  would 
be  spent  on  spotted  fever  in  1902,  and  that  the  county  commissioners 
of  Missoula  and  RavaUi  counties,  where  the  disease  was  localized, 
should  endeavor  to  raise  the  funds  needed  for  further  research  in 
1903.^^ 

Faced  with  the  possibility  of  no  further  state  support  for  their  medical 
crisis,  the  commissioners  of  RavaUi  County  appropriated  $400  in  April 
1903  for  continued  investigations.  They  added  a  caveat,  however, 
stipulating  that  Missoula  County  must  raise  a  matching  amount.  The 
commissioners  of  Missoula  County  balked,  according  to  newspaper 
accounts,  because  they  beHeved  that  spotted  fever  was  "more  than  a 
two  county  problem."  It  was  also  widely  believed  that  the  Montana 
congressional  delegation  could  persuade  the  U.S.  Public  Health  and 
Marine  Hospital  Service  to  fund  and  conduct  the  investigation.^^ 

With  its  sparse  population,  Montana  was  allocated  only  one  seat 
in  the  U.S.  House  of  Representatives  and,  of  course,  two  Senate  seats. 
This  three-man  delegation,  comprised  of  Congressman  Joseph  M. 
Dixon,  who  later  became  governor  of  the  state,  and  Senators  William 


36 


Rocky  Mountain  Spotted  Fever 


A.  Clark  and  Paris  Gibson,  actively  pressed  the  case  and  did  indeed 
persuade  Surgeon  General  Walter  Wyman  to  continue  federally  spon- 
sored research  into  spotted  fever.  The  Service  officer  Wyman  chose  to 
study  spotted  fever  in  1903  w^as  Passed  Assistant  Surgeon  John  F. 
Anderson,  w^ho  had  demonstrated  such  competence  in  research  that 
in  1902,  at  age  twenty-nine,  he  had  been  named  assistant  director  of 
the  Service's  Hygienic  Laboratory.  A  Virginian,  Anderson,  after  com- 
pleting medical  school,  had  done  graduate  v^ork  in  bacteriology  in 
Europe,  including  a  period  at  the  School  of  Tropical  Medicine  in 
Liverpool,  where  he  studied  protozoan  organisms  similar  to  the  pre- 
sumed agent  of  spotted  fever.^^ 

Anderson  left  Washington  on  24  April,  stopping  in  Great  Falls, 
Montana,  to  confer  with  the  secretary  of  the  Montana  State  Board  of 
Health,  A.  F.  Longeway;  then  he  continued  on  to  Missoula,  where  he 
was  offered  the  use  of  laboratories  at  the  University  of  Montana  and 
at  the  Northern  Pacific  Hospital.  He  decided  to  make  his  headquarters 
at  the  Northern  Pacific  in  order  to  work  closely  with  Wilson  and 
Chowning,  who  had  returned  for  an  additional  month's  work  in  1903. 
The  Minnesota  researchers  shared  their  data  with  Anderson  and  stud- 
ied five  new  cases  of  spotted  fever,  performing  one  autopsy.  Anderson, 
whom  they  taught  to  stain  the  sHdes  of  blood  in  order  to  see  the 
organism  they  had  described,  believed  he  saw  two  of  the  three  forms 
Wilson  and  Chowning  had  described.  "I  was  unable  to  find  the  paired 
form  in  stained  preparations,"  he  later  wrote,  "though  Drs.  Wilson 
and  Chowning  informed  me  that  they  had  no  difficulty  in  doing  so." 
Anderson  also  collected  specimens  of  the  ticks  suspected  of  being 
infected  with  spotted  fever  and  sent  them  to  the  Hygienic  Laboratory 
for  identification  by  Charles  Wardell  Stiles,  director  of  the  laboratory's 
Division  of  Zoology. 

Like  Cobb  before  him,  Anderson  was  convinced  that  Wilson  and 
Chowning  had  identified  the  spotted  fever  organism  and  that  their 
theory  of  tick  transmission  was  correct.  Upon  returning  to  Washington, 
Anderson  published  a  lengthy  report  on  spotted  fever  in  a  Bulletin  of 
the  Hygienic  Laboratory.  It  recapitulated  Wilson  and  Chowning's  work 
and  included  their  case  histories  and  maps."^^  Anderson  also  inserted 
photographs  and  drawings  of  the  eruption  of  the  disease,  which  he 
proposed  be  called  tick  fever  instead  of  spotted  fever  because  the  latter 
name  was  frequently  identified  with  typhus  and  cerebrospinal  men- 
ingitis. The  only  point  on  which  Anderson  disagreed  with  Wilson  and 
Chowning  had  to  do  with  the  ground  squirrel  as  the  probable  host  in 
nature.  Knowing  that  the  Piroplasma  of  Texas  cattle  fever  would  not 


The  Beginning  of  Scientific  Investigations 


37 


infect  sheep  nor  would  the  Piroplasma  of  dogs  infect  cats,  Anderson 
doubted  that  a  Piroplasma  of  ground  squirrels  would  easily  infect 
humans.  Because  of  his  skepticism  about  this  hypothesis,  Anderson 
omitted  any  mention  of  the  ground  squirrel  from  his  report."^^ 

Satisfied  that  their  1903  investigation  had  confirmed  the  work  of 
1902,  however,  Wilson  and  Chowning  also  collaborated  on  a  detailed 
scientific  article,  pubHshed  in  1904  in  the  premiere  issue  of  the  Journal 
of  Infectious  Diseases.  Entitled  "Studies  in  Pyroplasmosis  Hominis 
('Spotted  Fever'  or  'Tick  Fever'  of  the  Rocky  Mountains),"  the  paper 
included  drawings  of  the  presumed  protozoan  organism  of  spotted 
fever  as  well  as  epidemiological,  pathological,  microscopic,  and  clinical 
evidence  supporting  the  tick  transmission  theory. 

Most  inhabitants  of  the  Bitterroot  Valley  accepted  the  scientific  ex- 
perts' verdict  that  the  tick  was  the  culprit  in  transmitting  spotted  fever. 
Because  ticks  were  so  pervasive  during  the  spring,  however,  implicating 
them  as  vectors  of  a  dread  disease  had  immediate  economic  conse- 
quences, especially  for  property  owners  and  sawmill  operators  on  the 
west  side  of  the  valley  where  the  infection  was  locafized.  One  observer 
noted: 

Economically,  I  think  it  safe  to  say  that  the  tick  theory  has  been  more  disastrous 
to  the  infected  region  than  the  disease  itself.  Ticks  are  so  common  it  is  nearly 
impossible  for  a  man  working  out  of  doors  to  avoid  their  bites,  while  at  the 
same  time  they,  if  causing  the  disease,  constitute  a  cause  so  tangible  and  real 
that  the  dissemination  of  this  hypothesis  excited  a  fear  closely  akin  to  terror. 
Land  values  were  affected,  probably  a  majority  of  the  people  on  the  west  bank 
of  the  Bitter  Root  River  desiring  to  sell  and  nobody  willing  to  buy.  Saw  mills 
have  been  unable  to  procure  a  sufficiency  of  hands,  and  some  families  have 
sacrificed  their  property  in  order  to  get  away  as  soon  as  possible.  People  who 
formerly  frequented  that  region  for  business  or  pleasure  could  in  most  instances 
not  now  be  induced  to  go  there,  except  on  most  urgent  business,  during  the 
tick  season. 

As  the  implications  of  this  natural  calamity  became  manifest,  civic 
leaders  attempted  to  ameliorate  the  situation  with  pragmatic  action. 
Taking  stock  of  what  was  known  about  the  disease,  its  tick  vector, 
and  the  ground  squirrel —or  gopher  as  it  was  commonly  known  — 
which  presumably  served  as  a  natural  reservoir,  they  suggested  that 
strong  measures  be  taken  to  rid  the  valley  of  these  threats.  "It  having 
been  demonstrated  that  the  woodtick  is  the  cause  of  the  so-called 
'spotted  fever,'  "  an  editorial  in  the  Western  News  counseled, 

it  would  seem  that  the  best  preventive  of  the  disease  would  be  to  put  the 
venomous  insect  out  of  business.  .  .  .  The  woodtick  frequents  localities  only 


38 


Rocky  Mountain  Spotted  Fever 


where  there  is  much  fallen  and  decayed  timber.  The  abandoned  settings  of 
long-forgotten  saw  mills  are  its  favorite  haunts.  These  tick-infested  localities 
should  be  scourged  with  flames.  ...  If  the  gopher  is  an  ally  of  the  woodtick, 
aiding  and  abetting  it  in  its  death  dealing  mission,  it  too  must  be  exterminated."*"* 

By  the  following  spring,  preventive  tactics  w^ere  widespread.  The 
Western  News  reported  in  April  1904  that  "farmers  in  the  vicinity  of 
Stevensville  and  points  throughout  the  valley  are  making  a  strong  effort 
this  year  to  rid  the  country  of  the  gopher  pest.  A  new  preparation  of 
poisoned  wheat  is  being  generally  used,"  the  article  continued,  "and 
farmers  all  through  the  valley  have  laid  in  a  big  supply.  The  big  increase 
in  the  number  of  these  destructive  spermophiles  has  alarmed  the  ranch- 
ers to  no  Httle  extent."  Some  farmers  believed,  so  the  reporter  noted, 
that  the  state  should  offer  a  bounty  of  five  cents  "for  the  scalp  of  every 
one  of  the  animals  exterminated.""^^  There  was,  however,  one  unfor- 
tunate side  effect  of  the  indiscriminate  use  of  poisoned  grain.  Farmers 
who  scattered  it  on  the  ground,  hoping  that  the  ground  squirrels  would 
eat  it,  often  found  that  it  killed  game  birds  instead. 

Another  approach  to  tick  and  gopher  control  was  the  burning  of 
brush  land.  Reportedly  done  on  the  recommendation  of  John  F.  An- 
derson, a  policy  of  spring  burning  was  supported  by  the  Forest  Reserve 
office.  "The  great  brooding  [sic]  places  of  the  wood  tick  and  gophers 
is  in  the  old  slash  and  cuttings  along  the  foothills,"  reported  the  su- 
pervisor of  the  Bitterroot  Forest  Reserve,  commenting  also  that  "more 
spring  burning  this  year  has  been  done  than  during  any  three  previous 
seasons. ""^^ 

Although  these  efforts  may  have  heartened  valley  residents  by  pro- 
viding a  means  to  strike  back  against  a  deadly  enemy,  it  was  impossible 
to  exterminate  all  wood  ticks.  Careful  and  frequent  examinations  of 
the  body  to  locate  any  ticks  that  had  attached  themselves  thus  became 
a  ritual  for  many  people.  The  Western  News  cautioned:  "Should  you 
be  bitten  by  a  woodtick,  treat  it  as  you  would  a  snake  bite.  Be  prompt 
in  applying  remedies  to  counteract  the  poison.  Don't  wait  until  the 
poison  has  permeated  the  entire  system  or  you  are  likely  to  remain 
dead  a  long  time.""^^ 

In  response  to  this  warning,  many  people,  especially  those  who 
worked  on  the  infected  west  side  of  the  river,  carried  small  bottles  of 
carbolic  acid  for  immediate  application  if  a  tick  was  found  attached 
to  them.  Joseph  Lister  had  popularized  this  chemical  in  the  late  nine- 
teenth century  by  using  it  successfully  to  kill  germs  in  the  operating 
room.  Since  Bitterroot  citizens  applied  the  mouth  of  the  bottles  to  their 
skin  directly  over  the  tick  bite,  however,  many  suffered  "small  round 
sores  from  undiluted  acid."  The  Ravalli  Republican  even  reported  that 


The  Beginning  of  Scientific  Investigations 


39 


on  one  occasion  the  cork  had  come  out  of  a  bottle  in  a  man's  pocket, 
"and  the  hot  stuff  burned  him  severely !"^^ 

Every  theory  regarding  the  cause  of  spotted  fever,  moreover,  w^as 
carefully  follow^ed  and  exploited  by  charlatans  hoping  to  profit  from 
the  fear  generated  by  the  disease.  During  the  heyday  of  the  melted 
snow^  water  theory,  for  instance,  a  number  of  people  claiming  to  be 
scientists  made  a  comfortable  living  testing  drinking  v^^ater  for  spotted 
fever  infection.  Within  two  weeks  of  Wilson  and  Chowning's  an- 
nouncement that  a  hematozoon  had  been  found  in  the  blood  of  victims, 
the  promoters  of  King's  sarsaparilla  capitalized  on  the  new  scientific 
evidence  to  advertise  their  product  as  a  treatment.  "Spotted  fever  has 
been  pronounced  a  blood  disease,"  the  advertisement  asserted.  "Use 
King's  sarsaparilla  and  you  are  exempt  not  only  from  spotted  fever, 
but  a  great  many  other  diseases. Two  years  later,  a  homeopathic 
physician  in  Missoula  known  only  as  Dr.  Glasgow  claimed  that  he 
had  cured  a  sixteen-year-old  boy  of  spotted  fever  within  a  few  days 
by  administering  oral  doses  of  "venom  from  a  dagger-headed  viper 
found  in  Brazil."  Capitalizing  on  this  post  hoc,  ergo  propter  hoc  ar- 
gument, Glasgow  advertised  in  the  Daily  Missoulian  that  his  unusual 
therapy  was  good  not  only  for  spotted  fever  but  also  in  cases  of 
"arthritis  and  spinal  conditions."  In  this  period  of  unrestrained  en- 
terprise, such  exploitation  was  rampant.  Not  until  1906,  with  the 
enactment  of  the  federal  Pure  Food  and  Drugs  Act,  were  the  worst 
abuses  curbed. 

Quack  treatments  for  spotted  fever  flourished,  of  course,  because 
the  orthodox  medical  profession  could  do  Httle  to  treat  the  disease. 
After  his  investigation  of  spotted  fever,  for  example,  John  F.  Anderson 
suggested  that  physicians  employ  quinine  therapy,  "in  large  doses, 
preferably  hypodermically,"  because  of  spotted  fever's  presumed  sim- 
ilarity to  malaria.  Except  for  this  strategy,  which  soon  proved  to  have 
no  beneficial  effect  and  perhaps  actually  harmed  patients,  Anderson 
could  only  describe  supportive  therapies:  strychnine,  whisky,  or  other 
appropriate  "cardiac  stimulants"  to  support  the  heart;  Dover's  pow- 
ders or  morphine  sulfate  to  relieve  the  severe  headache;  large  quantities 
of  water  to  flush  out  the  kidneys;  and  warm  sponge  baths  to  reduce 
the  fever  and  refresh  the  patient.^^ 

At  the  conclusion  of  the  1903  tick  season,  it  seemed  even  more 
probable  than  in  1902  that  the  wood  tick  was  indeed  the  vector  of 
spotted  fever,  but  for  all  the  monies  and  time  expended,  no  effective 
cure  or  prevention  had  been  found.  The  Montana  State  Board  of  Health 
was  beleaguered  by  other  pubHc  health  problems,  especially  nonco- 
operation  from  physicians  who  refused  to  report  and  enforce  quar- 


40 


Rocky  Mountain  Spotted  Fever 


antines  for  designated  infectious  diseases,  such  as  measles.  Secretary 
A.  F.  Longeway,  moreover,  seemed  reluctant  to  enforce  the  board's 
rules  vigorously/^  Possibly  because  of  this,  w^hen  the  board  met  on  5 
May  1903,  Longew^ay  v^as  replaced  as  secretary  by  Thomas  D.  Tuttle/"^ 
The  thirty-three-year-old  Tuttle  w^as  a  Missouri  native  v^ho  had 
migrated  to  Montana  after  completing  his  medical  studies  in  1892  at 
the  College  of  Physicians  and  Surgeons  in  New  York/^  His  initial 
activities  and  reports  to  the  board  revealed  an  energetic,  no-nonsense 
approach  to  public  health/^  Shortly  after  taking  office,  for  example, 
Tuttle  sought  out  Anderson  and  Chov^ning  in  Missoula  to  gather 
information  on  the  spotted  fever  situation.  'T  visited  the  bacteriologists 
investigating  the  'Spotted  Fever'  in  the  Bitter  Root  Valley,"  Tuttle  stated 
in  his  July  quarterly  report,  "but  was  unable  to  learn  that  they  had 
made  any  progress  over  the  work  accomplished  last  year."  Realizing 
how  little  state  money  would  be  available  to  continue  investigations, 
Tuttle  wrote  in  early  February  1904  to  Senator  Paris  Gibson  and 
Congressman  Joseph  M.  Dixon  of  Montana  for  assistance  in  per- 
suading the  U.S.  Public  Health  and  Marine  Hospital  Service  to  continue 
researching  the  disease.  On  1 5  February  he  received  a  wire  from  Dixon 
stating  that  Anderson  and  another  expert  would  be  detailed  to  Mon- 
tana in  March.  When  neither  researcher  had  appeared  by  mid  April, 
Tuttle  again  wrote  Dixon,  "asking  him  to  hurry  the  matter  along," 
since  the  spotted  fever  season  had  already  begun  and  would  end  within 
three  months. 

Surgeon  General  Walter  Wyman  responded  by  sending  Montana  his 
most  experienced  researcher  in  protozoan  diseases,  Charles  Wardell 
Stiles,  who  had  joined  the  Hygienic  Laboratory  in  1902  as  the  first 
director  of  the  newly  created  Division  of  Zoology.  Stiles  had  taken  his 
Ph.D.  in  zoology  in  1 890  with  the  distinguished  Leipzig  helminthologist 
Rudolph  Leuckart  and  from  1891  to  1902  had  served  as  principal 
zoologist  for  the  Bureau  of  Animal  Industry  in  the  U.S.  Department 
of  Agriculture,  where  he  worked  alongside  Theobald  Smith  and  F.  L. 
Kilbourne,  discoverers  of  the  Texas  cattle  fever  piroplasma.  Shortly 
before  joining  the  U.S.  Public  Health  and  Marine  Hospital  Service, 
Stiles  had  won  considerable  fame  by  identifying  a  new  species  of 
hookworm  and  correctly  deducing  that  it  rather  than  malaria  caused 
the  anemia  prevalent  in  the  southern  United  States.  For  this  work  he 
had  been  hailed  as  the  discoverer  of  the  "Germ  of  Laziness. "^^  Surgeon 
General  Wyman  hoped  that  Stiles  would  be  able  to  trace  the  hfe  cycle 
of  the  parasite  that  caused  spotted  fever,  study  the  tick  that  transmitted 
it  and  the  ground  squirrels  that  harbored  the  disease  in  nature,  and 
arrive  at  a  workable  means  of  preventing  the  disease. 


The  Beginning  of  Scientific  Investigations 


41 


In  1904,  Charles  Wardell  Stiles,  director  of  the  Division  of  Zoology  at  the 
Hygienic  Laborator)^  of  the  U.S.  PubUc  Health  and  Marine  Hospital  Ser- 
vice, refuted  Wilson  and  Chowning's  assertion  that  a  protozoan  organism 
caused  spotted  fever.  Because  of  widespread  assumptions  about  microor- 
ganisms and  their  arthropod  vectors,  Stiles  concluded  that  the  disease  was 
not  transmitted  by  ticks.  (Courtesy  of  the  National  Library  of  Medicine.) 


With  his  strong  background  in  zoological  subjects,  Stiles  was  pre- 
disposed to  look  favorably  on  the  findings  of  Anderson  and  Wilson 
and  Chowning.  In  fact,  Stiles  looked  upon  the  biological  transmission 
of  protozoa  by  arthropods  as  a  law  of  nature  rather  than  a  working 
hypothesis.  In  April  1901,  when  he  had  presented  the  annual  Toner 
Lecture,  which  he  titled,  "Insects  as  Disseminators  of  Disease,"  at 
Georgetown  University,  Stiles  had  stated: 

We  may  lay  down  two  general  biologic  rules,  which,  I  believe,  are  enunciated 
tonight  for  the  first  time:  The  first  rule,  to  which  at  present  a  few  exceptions 
are  known,  is  that  diseases  which  are  accidentally  spread  by  insects  are  caused 
by  parasitic  plants,  particularly  bacteria.  The  second,  to  which  no  exceptions 


42 


Rocky  Mountain  Spotted  Fever 


are  as  yet  known,  is  that  those  diseases  which  are  dependent  upon  insects  or 
other  arthropods  for  their  dissemination  and  transmission  are  caused  by  par- 
asitic animals,  particularly  by  sporozoa  and  worms.^^ 

After  working  in  the  Bitterroot  from  7  May  to  6  July,  however, 
during  which  time  he  saw  ten  patients,  drew  blood  samples  from  nine, 
attended  an  autopsy  on  one,  and  conducted  more  than  one  hundred 
hours  of  work  at  the  microscope.  Stiles  completely  changed  his  mind 
about  the  earlier  work.^^  He  could  find  no  trace  of  the  reported  or- 
ganism in  the  blood  of  spotted  fever  victims.  In  his  microscopic  work, 
Stiles  was  joined  by  U.S.  Army  physician  Percy  M.  Ashburn,  who  was 
investigating  the  disease  under  orders  from  the  surgeon  general  of  the 
army.  The  two  men  worked  independently  but  met  almost  daily  to 
compare  notes.  "I  used  daylight,  lamplight  and  electric  light,"  Stiles 
wrote,  "dry  and  oil  lenses  of  Zeiss,  Spencer,  Leitz,  and  Bausch  & 
Lomb.  The  specimens  were  taken  at  regular  and  irregular  intervals, 
day  and  night,  from  both  fatal  and  non-fatal  cases."  Stiles  and  Ashburn 
then  consulted  with  Chowning,  who  was  in  the  Bitterroot  Valley  at 
that  time,  but  Chowning  was  unable  to  demonstrate  the  Piroplasma 
in  the  blood.^^ 

"Accordingly,"  wrote  Stiles,  "the  work  of  1904  has  failed  to  confirm 
the  conclusions  of  1902  and  1903,  and  indications  are  not  lacking 
that  at  least  some  of  the  stages  of  the  supposed  Piroplasma  hominis 
consist  in  reality  of  vacuoles,  blood  platelets,  blood  dust,  artifacts,  and 
tertian  malaria  parasites. "^^  Later  in  the  year,  another  U.S.  Army  phy- 
sician, Charles  F.  Craig,  who  had  considerable  experience  investigating 
tropical  diseases,  reported  in  American  Medicine  the  results  of  his  own 
"most  careful  study  of  the  subject."  Confirming  the  findings  of  Ashburn 
and  Stiles,  Craig  suggested  that  "Chowning,  Wilson,  and  Anderson 
.  .  .  have  mistaken  areas  devoid  of  hemoglobin  in  the  red  cell  ...  for 
a  protozoan  parasite. "^"^ 

The  evidence  seemed  overwhelming  that  no  Piroplasma  was  present. 
Such  organisms,  however,  were  often  difficult  to  find  under  the  mi- 
croscope, so  Stiles  attempted  to  determine  the  presence  of  the  organism 
by  indirect  means— by  comparing  symptoms  of  spotted  fever  with 
symptoms  of  known  piroplasmic  maladies,  especially  Texas  cattle  fe- 
ver. When  he  applied  his  wide  knowledge  of  piroplasmic  diseases  in 
a  comparison  with  spotted  fever,  however,  he  found  few  similarities. 
Most  known  piroplasmic  diseases  flourished  in  swampy  valleys,  but 
spotted  fever  occurred  in  the  foothills  of  the  Bitterroot  Mountains. 
Piroplasmic  diseases  were  also  "apt  to  attack  large  numbers  of  patients 
at  about  the  same  time  in  the  same  locality,"  Stiles  noted,  and  "if 
'spotted  fever'  is  a  piroplasmosis,  transmitted  by  a  tick,  we  should 


The  Beginning  of  Scientific  Investigations 


43 


expect  a  large  number  of  cases  to  develop  in  any  locality  in  which  one 
case  develops.  This,  hov^ever,  is  exactly  what  we  do  not  find  in  'spotted 
fever.'  "  This  observation,  he  admitted,  "was  the  first  point  to  lead  me 
to  seriously  doubt  the  tick  hypothesis. "^^ 

Stiles  continued,  comparing  one  point  after  another  about  spotted 
fever  and  known  piroplasmoses.  No  known  protozoan  disease  was 
characterized  by  a  rash,  but  in  spotted  fever  the  rash  was  the  principal 
diagnostic  sign.  Victims  of  piroplasmosis  normally  became  emaciated; 
victims  of  spotted  fever  appeared  well  nourished.  In  Texas  fever  the 
organism  caused  the  blood  to  become  "thin,  watery,  and  pale,"  while 
the  blood  of  spotted  fever  victims  became  "thick,  molasses  like,  and 
dark."  The  bile  in  piroplasmosis  became  thickened,  but  in  spotted 
fever  the  bile  remained  fluid.^^  Stiles  concluded  that  the  disease  was 
not  a  piroplasmosis.  The  tick  transmission  theory  and  its  corollary, 
the  ground  squirrel  host,  were  totally  dependent,  in  Stiles's  thinking, 
on  the  presence  of  protozoan  organisms.  "An  important  point  upon 
which  I  desire  to  place  considerable  stress,"  he  stated,  "is  that  the  tick 
theory  is  a  secondary  hypothesis  based  upon  the  idea  that  'spotted 
fever'  is  caused  by  a  protozoon.  If  the  Piroplasma  theory  is  correct, 
the  tick  theory  immediately  receives  a  very  strong  argument  in  its 
favor,  for  other  species  of  Piroplasma  are  known  to  have  ticks  as  their 
intermediate  host."^^ 

From  his  work  in  1904,  Stiles  concluded  that  the  earlier  investigators 
had  been  wrong  about  the  causative  organism,  about  the  tick  trans- 
mission theory,  and  about  the  ground  squirrel  host.  His  own  inves- 
tigation, however,  yielded  entirely  negative  results,  for  he  produced 
"no  new  theories  .  .  .  regarding  the  cause,  transmission,  and  origin  of 
this  disease. "^^ 

Although  lacking  evidence.  Stiles  offered  some  speculation  about 
alternative  causes  that  was,  as  he  said,  "in  accord  with  the  generally 
accepted  view"  regarding  arthropods  and  disease.  If  spotted  fever  were 
not  a  protozoan  disease,  he  reasoned,  it  must  be  a  bacterial  disease. 
If  it  were  bacterial,  it  would  probably  be  contagious.  Supporting  Stiles's 
contention,  moreover,  Percy  M.  Ashburn  cited  the  cases  of  Mrs.  Robert 
Allen,  a  twenty-eight-year-old  housewife,  and  Miss  Helen  McConnon, 
a  twenty-four-year-old  schoolteacher,  both  of  whom  insisted  that  be- 
cause of  heightened  awareness  that  ticks  might  spread  the  disease,  they 
had  meticulously  examined  their  bodies  daily  and  had  not  been  bitten 
by  ticks  before  the  onset  of  spotted  fever.^^  Such  evidence  suggested 
to  Stiles  and  Ashburn  that  contagion  might  be  present.  "It  seems  to 
me,"  Stiles  wrote,  "that  the  possibility  is  by  no  means  excluded  that, 
despite  the  general  experience  regarding  the  noncontagiousness  of  the 


44 


Rocky  Mountain  Spotted  Fever 


disease,  such  close  intimacy  as  sleeping  in  the  same  bed  might  perhaps 
result  in  a  transmission  of  the  disease  to  a  healthy  individual. 

Stiles  also  attempted  to  explain  the  seasonal  occurrence  of  spotted 
fever  within  the  existing  theoretical  framew^ork.  "Practically  all  authors 
lay  stress  upon  the  fact  that  the  affection  under  discussion  is  preem- 
inently a  disease  of  the  spring  months,"  Stiles  did  not,  however,  relate 
the  emergence  of  ticks  to  spring  warming,  but  he  did  note  the  con- 
nection between  the  coming  of  spring  and  a  rise  in  the  amount  of 
water  in  streams  from  melted  snow.  In  fact,  he  revived  the  old  theory 
that  melted  snow  water  might  be  a  source  of  infection.  "Such  as  the 
data  are,"  he  said,  "they  tend  to  support  rather  than  to  negative  [sic] 
the  popular  idea  that  the  melting  snow  has  some  direct  or  indirect 
connection  with  the  development  of  cases,  or  . . .  that  conditions  which 
favor  the  melting  of  the  snow  also  favor  the  appearance  of  cases  of 
spotted  fever."^^ 

When  he  returned  to  Washington,  Stiles  published  the  most  lengthy 
report  on  spotted  fever  yet  produced.  In  addition  to  his  scientific 
conclusions,  he  added  an  observation  that  would  be  used  to  question 
his  integrity  in  later  years.  "The  tick  theory  has  caused  serious  financial 
loss  to  the  Bitter  Root  Valley  and  has  produced  an  effect  which  in  a 
few  cases  had  bordered  on  hysteria.  In  justice  to  the  property  interests 
of  the  valley  and  the  peace  of  mind  of  the  inhabitants,  I  think  no  time 
should  be  lost  in  publishing  the  statement  that  the  results  of  study  this 
year  have  absolutely  and  totally  failed  to  confirm  this  hypothesis. "^^ 
This  statement  inspired  one  author  to  suggest  that  Stiles  succumbed, 
at  least  unconsciously,  to  pressure  from  Bitterroot  residents  who  re- 
jected the  tick  theory  because  of  the  damage  it  had  already  done  to 
their  property  values. Such  an  interpretation  misses  the  clear  intel- 
lectual motivation  behind  Stiles's  rejection  of  the  tick  hypothesis  and 
ignores  the  responsibilities  of  government  scientists  in  the  Progressive 
era. 

Stiles,  like  other  employees  of  government  agencies,  had  to  be  re- 
sponsive to  the  concerns  of  his  employers— the  taxpayers  of  the  United 
States.  As  James  H.  Cassedy  has  noted  in  his  analysis  of  Stiles's  hook- 
worm activities  during  this  same  period,  such  an  awareness  did  not 
compromise  a  scientist's  integrity,  but  it  made  him  think  twice  before 
publishing  findings  that  could  have  a  potentially  negative  economic 
impact.  Like  most  other  government  scientists  during  the  Progressive 
era,  Stiles  was  not  doctrinaire  on  major  political  or  social  issues.  For 
instance,  in  1896  he  strongly  supported  the  extension  of  governmental 
authority  to  regulate  filthy  country  slaughterhouses.  He  had  also  been 
willing,  however,  to  apply  his  knowledge  on  behalf  of  U.S.  pork  prod- 


The  Beginning  of  Scientific  Investigations 


45 


ucers  in  1898,  when  German  restrictions  on  pork  allegedly  contami- 
nated with  trichinosis  threatened  their  livelihoods/"^  As  a  government- 
employed  professional,  Stiles  could  warn  his  colleagues  that  "diseases 
have  an  economic  as  well  as  an  academic  side,"  and  caution  them:  "If 
it  can  be  foreseen  that  a  given  working  hypothesis  is  calculated  to 
result  in  financial  loss  to  an  infected  district,  such  hypothesis  should 
be  subjected  to  most  searching  criticism  before  it  is  published.  And  if 
it  can  be  foreseen  that  any  good  to  be  accomplished  by  its  announce- 
ment is  far  outweighed  by  its  probable  evil  effects,  its  publication 
should  be  postponed  until  its  correctness  is  demonstrated  or  is  beyond 
reasonable  doubt."^^  In  a  period  when  the  status  and  authority  of 
experts  were  increasing,  it  was  the  opinion  of  Stiles's  zoological  col- 
leagues that  mattered  to  him,  but  when  he  found  no  evidence  of  tick 
transmission  of  spotted  fever,  he  felt  duty  bound  to  correct  the  eco- 
nomic hardship  produced  by  the  "premature"  conclusions  about  ticks 
and  the  disease  published  by  Wilson  and  Chowning. 

The  results  of  the  work  of  Stiles,  Ashburn,  and  Craig,  coming  at 
the  end  of  two  seasons  of  vigorous  tick  and  gopher  control  efforts, 
left  valley  residents  more  mystified  than  ever  about  their  strange  dis- 
ease. The  elegance  of  the  Piroplasma-tick-gopher  hypothesis  had  seem- 
ingly been  destroyed  by  the  "ugly  little  fact"  that  no  Firoplasma  existed. 
The  intellectual  model  that  Hnked  only  protozoan  organisms  to  ar- 
thropod transmission,  moreover,  held  such  control  over  the  thinking 
of  the  research  community  that  no  one  seems  to  have  considered  the 
possibility  that  some  other  organism  might  be  transmitted  by  the  ticks. 
No  one  even  attempted  to  verify  tick  transmission  of  the  disease  as  a 
separate  experiment.^^  Doubtless  the  scientific  stature  of  Stiles,  of  army 
surgeon  Ashburn,  and  of  Craig,  who  had  distinguished  himself  in 
tropical  diseases  during  the  Spanish-American  War,  added  considerable 
authority  to  their  conclusions  about  spotted  fever. 

Although  the  spotted  fever  question  was  an  intriguing  intellectual 
problem  for  these  men,  they  were  not  insensitive  to  the  desire  of  valley 
residents  for  some  means  to  combat  the  disease,  which  continued  to 
claim  victims  each  spring.  In  1904  local  newspapers  reported  fourteen 
cases  of  spotted  fever  and  documented  ten  deaths.  Among  those  who 
died  was  John  Rankin,  an  early  Missoula  County  pioneer  whose  daugh- 
ter Jeanette  later  served  as  a  congresswoman  from  Montana. Percy 
M.  Ashburn  suggested  a  new  approach  to  treatment,  basing  his  notions 
on  the  presumption  that  a  toxin-producing  bacterium  was  possibly 
the  cause  of  the  disease.  Employing  an  analogy  with  typhoid  fever, 
Ashburn  stated  that  "the  grave  symptoms"  were  probably  produced 
by  "a  powerful  toxin  circulating  in  the  blood;  and  the  fact  that  we 


46 


Rocky  Mountain  Spotted  Fever 


do  not  know  the  maker  of  the  poison  should  not  deter  us  from  trying 
to  ehminate  it  and  to  strengthen  and  sustain  these  parts  and  functions 
especially  injured  by  it,  until  the  organism  has  time  to  form  the  proper 
antibodies  in  sufficient  amount  to  overcome  the  disease. "^^ 

What  Ashburn  suggested  was  the  use  of  hydrotherapy,  or  water 
treatment,  popularized  by  Simon  Baruch  and  John  Harvey  Kellogg 
and  recommended  in  1892  as  a  treatment  for  typhus  by  the  distin- 
guished Johns  Hopkins  physician,  WiUiam  Osler/^  Under  the  hydro- 
therapeutic  regimen  that  Ashburn  suggested,  the  patient  was  to  be 
bathed  in  cold  water  at  70°  F  for  ten  to  twenty  minutes,  while  the 
attending  nurse  or  physician  constantly  applied  "hand  friction  to  the 
body  and  limbs,  with  cold  applications  to  the  head."  This  procedure 
was  to  be  repeated  every  three  hours  as  long  as  the  patient's  temperature 
remained  above  102.5°  F.  In  difficult  cases,  ice  water  enemas,  given 
while  the  patient  drank  alcohol  or  hot  coffee  — both  considered  stim- 
ulants—were said  to  increase  the  "efficiency  of  the  bath  and  hasten 
the  reaction."  The  theoretical  basis  of  hydrotherapy  rested  on  the 
observation  that  cold  water  and  friction  produced  at  first  a  contraction 
of  the  blood  vessels  followed  by  their  dilation,  which  brought  blood 
to  the  surface  of  the  body  where  the  heat  of  a  fever  might  more  readily 
be  dispersed.  "Quite  possibly,"  Ashburn  opined,  "by  so  keeping  up 
the  tone  of  the  peripheral  vessels  from  the  beginning  of  the  disease 
they  might  be  saved  from  the  degeneration"  that  permitted  hemmor- 
rhages  into  the  skin  and  caused  "the  darkening  of  the  spots."  Re- 
portedly this  cold  water  treatment  was  routinely  employed  in  spotted 
fever  cases  by  some  Bitterroot  physicians. ^° 

In  the  space  of  three  years,  the  seasons  of  1902,  1903,  and  1904, 
scientific  investigations  of  spotted  fever  had  been  launched,  but  the 
inconclusive  results  revealed  only  that  the  disease  remained  an  enigma. 
Noting  the  muddled  picture  that  emerged  from  the  investigations  of 
Wilson  and  Chowning,  Anderson,  Stiles,  and  Ashburn,  an  editorial  in 
the  Journal  of  the  American  Medical  Association  deplored  the  fact 
that  the  cause  "of  this  strange  disease  is  as  obscure  as  ever,"  and  called 
for  a  continuation  of  the  investigation.  "Further  investigation  is  of 
great  importance,  not  only  from  a  scientific  view  but  also  from  an 
economic  point  of  view.  The  tick  theory  of  the  disease  seems  to  have 
reduced  the  inhabitants  almost  to  a  state  of  panic,  and  it  is  hoped  that 
the  disease  will  be  reinvestigated  ...  if  only  to  reassure  them  and  to 
render  the  development  of  this  fertile  valley  practicable."^^ 


Chapter  Four 


Dr.  Ricketts's  Discoveries 

Most  of  the  knowledge  and  much  of  the  genius  of  the  research  worker  lie 
behind  his  selection  of  what  is  worth  observing.  It  is  a  crucial  choice,  often 
determining  the  success  or  failure  of  months  of  work,  often  differentiating 
the  brilliant  discoverer  from  the  plodder. 

Alan  Gregg,  The  Furtherance  of  Medical  Research 


By  1905  advances  in  many  fields  of  science  and  technology  were 
making  tangible  changes  in  American  life.  X-rays,  for  example,  dis- 
covered just  before  the  turn  of  the  century,  were  already  revolutionizing 
the  practice  of  medicine.  Similarly,  if  more  gradually,  the  advent  of 
electric  Hghts,  telephones,  automobiles,  phonographs,  and  vacuum 
cleaners  was  altering  the  daily  lives  of  thousands  of  citizens.^  During 
this  so-called  Progressive  era,  optimism  nourished  by  faith  in  the  prom- 
ise of  science  also  spurred  reform  movements  to  improve  industrial 
slum  conditions,  to  conserve  natural  resources,  and  to  curb  the  abuses 
of  unbridled  capitalism.  In  the  Bitterroot  Valley  of  Montana,  however, 
boosters  hoping  to  attract  new  residents  may  have  harbored  doubts 
about  the  efficacy,  or  at  least  the  efficiency,  of  science.  The  results  of 
three  years'  work  by  highly  regarded  scientific  experts  had  failed  to 
uncover  the  cause  of  the  valley's  terrifying  affliction,  spotted  fever.  Yet 
the  stalemate  produced  by  conflicting  theories  was  not  a  defeat  but 
an  indication  that  a  new  approach  was  needed.  Beginning  in  1906, 
valley  residents  would  witness  rapid  progress  in  spotted  fever  inves- 
tigations as  researchers,  especially  Howard  Taylor  Ricketts  of  the  Uni- 
versity of  Chicago,  studied  past  findings  and  explored  the  question 
from  new  directions. 

In  June  1904  the  secretary  of  the  Montana  State  Board  of  Health, 
Thomas  D.  Tuttle,  attended  the  second  annual  meeting  of  state  and 
territorial  health  officers  with  the  surgeon  general  of  the  U.S.  Public 
Health  and  Marine  Hospital  Service  to  lobby  for  continued  investi- 
gations of  spotted  fever  by  the  federal  government.  Noting  enthusi- 
astically in  his  report  to  the  board  the  "hundreds  of  little  points" 


47 


48 


Rocky  Mountain  Spotted  Fever 


regarding  health  work  he  obtained  at  the  meeting,  Tuttle  related  the 
considerable  interest  that  Montana's  "unknown"  disease  engendered 
in  other  delegates.  Most  importantly,  Tuttle  announced  that  he  had 
convinced  Surgeon  General  Wyman  to  continue  supporting  spotted 
fever  research  until  the  nature  of  the  disease  was  positively  determined. 
This  commitment,  Tuttle  noted,  was  well  worth  the  cost  of  his  trip, 
since  it  might  stem  the  plunge  of  property  values  in  the  Bitterroot.^ 

The  confusion  generated  by  the  conflicting  reports  of  Wilson  and 
Chowning,  Anderson,  Stiles,  and  Ashburn  about  the  germ  of  spotted 
fever,  and  especially  about  the  tick  as  a  vector  of  the  disease,  had 
indeed  jeopardized  property  values  on  the  west  side  of  the  valley.  This 
threat  appeared  just  as  the  Bitterroot  launched  a  major  effort  to  expand 
its  economy  by  developing  an  irrigation  system  that  would  open  the 
benchlands— the  dry  shores  of  the  ancient  lake  bed— to  cultivation. 
Since  the  mid  1890s,  valley  residents  had  sold  their  apples  commer- 
cially, claiming  that  the  climate  in  the  Bitterroot  was  ideal  for  producing 
the  tart,  flavorful  Mcintosh  Red  apple.  In  a  period  before  dry  farming 
was  employed,  however,  the  waterless  bench  lay  barren.  In  1905  a 
group  of  Chicago  financiers  developed  a  scheme  to  irrigate  west  side 
benchlands,  a  plan  that  was  soon  expanded  into  an  enormous  irrigation 
project  to  bring  water  to  the  east  side  bench  as  well.  Locally  the 
proposed  irrigation  canal  and  flume  were  called  the  Big  Ditch.  Ad- 
vertising in  Chicago  newspapers,  the  plan's  promoters  offered  potential 
buyers  a  bearing  orchard  and  a  contract  with  Bitterroot  citizens  who, 
during  the  first  five  years  of  ownership,  would  tend,  harvest,  and  market 
the  apples  for  10  percent  of  the  net  profit.  By  1907  land  in  the  Bitterroot 
was  selling  for  $100— $150  an  acre.^ 

Spotted  fever  represented  a  distinct  menace  to  this  enterprise,  which 
was  expected  to  swell  the  population  of  the  Bitterroot  nearly  tenfold 
as  new  orchards  came  under  cultivation.  Since  scientific  research  had 
produced  no  cure  and  much  confusion,  local  Bitterroot  boosters 
adopted  the  tactic  of  officially  ignoring  the  disease's  existence.  Begin- 
ning in  1904,  newspapers  rarely  mentioned  spotted  fever  in  obituaries, 
usually  describing  it  as  fever  or  a  brief  illness.  Distinguishing  spotted 
fever  cases  from  other  maladies  in  news  accounts  thus  became  much 
more  difficult.  Only  the  time  of  year  and  the  duration  of  the  disease 
provided  clues.  Because  few  states  at  this  time  monitored  any  but  the 
most  contagious  diseases,  the  Bitterroot  Valley  suffered  no  official 
reprimand  for  such  action.  Spotted  fever  was  not  one  of  the  reportable 
diseases— those,  such  as  diphtheria,  smallpox,  and  typhoid  fever,  that 
physicians  were  obligated  to  report  to  state  health  authorities.  Vital 
statistics  on  births  and  deaths  in  the  state  were  not  even  required  to 


Dr.  Ricketts's  Discoveries 


49 


be  collected  until  mid  1907,  and  Montana  preceded  many  other  states 
in  that  endeavor."^ 

Despite  this  vote  of  no  confidence  in  science  by  local  residents,  in 
1905  research  into  spotted  fever  reached  a  turning  point.  Montana 
Congressman  Joseph  M.  Dixon  and  the  State  Board  of  Health  secretary, 
Thomas  D.  Tuttle,  held  Surgeon  General  Walter  Wyman  to  his  promise 
to  continue  investigating  the  disease.  Tuttle  sent  a  written  request  and 
Dixon  visited  the  surgeon  general.  At  the  beginning  of  May,  Edw^ard 
Francis,  a  Hygienic  Laboratory  physician  v^ho  had  contributed  to  the 
Service's  study  of  yellow^  fever  in  Vera  Cruz,  Mexico,  v^as  detailed  to 
Montana.^  Fifteen  years  later,  Francis  w^ould  make  a  significant  con- 
tribution to  the  understanding  of  tularemia,  another  disease  of  nature 
found  in  the  Bitterroot  and  in  other  areas,  but  in  1905  his  research 
on  spotted  fever  produced  no  significant  results.  Although  he  corrob- 
orated Stiles's  findings  that  no  Piroplasma  was  present,  Francis  was 
unable  to  throw  further  light  on  the  etiology  of  the  disease  and  never 
published  an  account  of  his  work.^  These  negative  findings,  however, 
indicated  that  the  next  spotted  fever  experiments  must  move  in  a 
different  direction  if  they  were  to  be  productive. 

In  November  1904,  Charles  Wardell  Stiles  unwittingly  fueled  this 
fire  when  he  delivered  the  Middleton  Goldsmith  Lecture,  an  address 
published  in  early  1905  in  the  highly  respected  and  widely  read  sci- 
entific journal.  Proceedings  of  the  New  York  Pathological  Society. 
Taking  as  his  title,  "Zoological  Pitfalls  for  the  Pathologist,"  Stiles 
cautioned  pathologists  to  be  careful  about  drawing  zoological  con- 
clusions if  they  were  not  thoroughly  trained  in  zoology.  He  held  up 
the  Piroplasma  theory  of  Wilson  and  Chowning  as  a  case  in  point, 
and  his  refutation  of  their  theories  "savored  of  scorn,"  as  one  observer 
noted.^ 

Stiles's  pointed  and  uncharitable  remarks  stung  Wilson  and  Chown- 
ing, but  they  also  stimulated  the  interest  of  other  investigators  in  the 
debate  over  this  mysterious  disease.  Louis  B.  Wilson  abandoned  spotted 
fever  research  in  1905  when  he  accepted  a  position  at  the  Mayo  Clinic. 
There  he  pursued  a  distinguished  career  as  a  pathologist  and  admin- 
istrator. William  M.  Chowning,  however,  continued  spotted  fever  in- 
vestigations while  engaging  in  his  newly  established  private  surgical 
practice.  He  hoped  to  justify  his  earHer  work  and  produce  an  antitoxin 
for  spotted  fever.  In  early  1906,  Chowning  corresponded  with  Howard 
Taylor  Ricketts,  a  pathologist  at  the  University  of  Chicago,  who  was 
interested  in  beginning  his  own  investigation  of  spotted  fever.  Although 
Chowning  had  hoped  that  the  two  might  work  together  despite  Stiles's 
adverse  criticism,  Ricketts  stipulated  that  his  would  be  an  independent 


50 


Rocky  Mountain  Spotted  Fever 


study.  "I  may  say,"  Ricketts  wrote,  "that  it  was  exactly  this  criticism 
of  Stiles  which  gave  me  the  idea  of  going  to  Montana  to  study  spotted 
fever.  I  was  not  at  all  pleased  with  the  tone  of  his  criticism  as  it  was 
presented  to  the  New  York  pathological  society,  and  it  occurred  to 
me  that  this  would  be  a  good  time  for  a  third  party  to  go  into  the 
field  and  repeat  the  ground  covered  by  yourself  and  Wilson."^ 

Chowning  also  revealed  that  he  had  "experimentally  reproduced" 
spotted  fever  in  a  human  in  Minneapolis  and  was  presently  "watching 
another  similar  inoculation."  The  material  used  "was  a  blood  (defi- 
brinated)  culture  from  a  Montana  case  (fatal)."  The  first  experimental 
case  was  recovering;  the  second  was  too  recent  to  predict.  Ricketts 
made  no  comment  to  Chowning  about  the  human  experiments,  and 
Chowning  never  published  the  results  of  this  daring  and  ethically 
questionable  investigation.  Neither  of  them  knew  that  Idaho  physicians 
had  also  conducted  tick  transmission  experiments  on  humans.  The 
ticks  used,  however,  were  infected  with  the  mild  Idaho  strain  of  the 
disease,  not  the  fatal  Bitterroot  strain  Chowning  used.  Although  this 
study  was  not  pubhshed  until  1908,  Lucien  P.  McCalla  and  his  col- 
league H.  A.  Brereton  had  in  May  1905  obtained  permission  from 
two  patients,  one  male  and  one  female,  to  attach  to  each  a  tick  that 
had  been  affixed  to  a  patient  suffering  from  Idaho  spotted  fever.  Both 
patients  became  ill  with  the  disease  and  both  recovered.^ 

Ricketts  was  undoubtedly  interested  in  Chowning's  proposed  an- 
titoxin against  spotted  fever,  for  this  was  an  area  in  which  Ricketts 
had  just  published  a  major  textbook,  Infection,  Immunity,  and  Serum 
Therapy.  This  promising  young  researcher,  born  in  Findley,  Ohio,  in 
1 871,  had  taken  his  undergraduate  degree  at  the  University  of  Ne- 
braska, where  he  studied  zoology  with  the  distinguished  animal  par- 
asitologist Henry  B.  Ward.  In  1894  he  had  entered  Northwestern 
University  School  of  Medicine  in  Chicago  as  a  member  of  the  second- 
year  class  because  of  his  soHd  undergraduate  preparation,  a  criterion 
many  of  his  classmates  lacked.  ^°  Despite  a  nervous  breakdown  from 
overwork  and  constant  financial  problems— his  family  had  lost  its 
fortune  in  the  panic  of  1893 —Ricketts  had  excelled  and  graduated  in 
1897,  winning  an  internship  at  Cook  County  Hospital.  In  1900  he 
became  a  fellow  in  pathology  and  cutaneous  diseases  at  Rush  Medical 
College  in  Chicago,  where  he  accomplished  his  first  important  research, 
a  study  of  blastomycosis,  the  first  disease  known  to  be  produced  by 
a  yeast. 

This  work  brought  him  to  the  attention  of  Ludvig  Hektoen,  who 
was  shortly  to  become  chairman  of  the  Department  of  Pathology  and 
Bacteriology  at  the  University  of  Chicago  and  director  of  the  John 


Dr.  Ricketts's  Discoveries 


51 


Howard  Taylor  Ricketts  of  the 
University  of  Chicago  designed 
the  experiment  that  first  demon 
strated  tick  transmission  of 
Rocky  Mountain  spotted  fever. 
Ricketts's  contributions  to  the 
understanding  of  spotted  fever, 
including  identification  of  the 
causative  organism,  were  later 
recognized  when  the  microorga 
nisms  that  cause  spotted  fever 
and  related  diseases  were  desig- 
nated Rickettsiae  in  his  honor. 
Ricketts  died  in  19 10  during  a 
study  of  epidemic  typhus  in 
Mexico.  (Courtesy  of  the  Na- 
tional Library  of  Medicine.) 

Rockefeller  McCormick  Memorial  Institute  for  Infectious  Diseases.  At 
Hektoen's  suggestion,  Ricketts  spent  a  year  abroad,  in  Berlin,  Vienna, 
and  Paris,  where  he  perfected  his  laboratory  technique  and  broadened 
his  understanding  of  theoretical  microbiology.  Upon  his  return  in  1902 
he  was  appointed  instructor  in  Hektoen's  department  at  Chicago.  With 
the  publication  of  his  book  in  1906,  Ricketts  had  established  his  rep- 
utation as  a  rising  scientific  star. 

Since  Montana  had  appropriated  no  additional  monies  in  1906  for 
spotted  fever  investigations,  the  three  researchers  who  appeared  in  the 
field  that  year  had  to  supply  their  own  funds.  Ricketts  obtained  a  small 
grant  from  the  Committee  on  Scientific  Research  of  the  American 
Medical  Association  (AMA)  to  defray  his  expenses.  He  arrived  on  21 
April  at  the  Northern  Pacific  Hospital  in  Missoula  and,  at  the  invitation 
of  the  chief  surgeon,  E.  W.  Spottswood,  erected  laboratory  and  personal 
housing  tents  on  the  hospital  grounds.  William  M.  Chowning  also 
worked  in  the  field  at  his  own  expense,  Hmiting  his  research  to  mi- 
croscopic analysis  of  the  blood  of  spotted  fever  victims.  Having  ap- 
parently abandoned  the  Piroplasma  theory,  Chowning  focused  instead 
on  what  he  described  as  "a  myriad  of  fantastic  but  highly  deceptive 
forms,"  which  he  classified  as  fungi. 


5  2  Rocky  Mountain  Spotted  Fever 


Interior  of  Howard  Taylor  Ricketts's  tent  laboratory,  erected  in  1906  in 
Missoula,  Montana.  (Used  by  permission  of  the  Department  of  Special 
Collections,  University  of  Chicago  Library.) 


Joining  Ricketts  and  Chowning  in  late  April  was  Walter  W.  King 
of  the  U.S.  Public  Health  and  Marine  Hospital  Service,  who,  fresh 
from  five  years'  service  as  chief  quarantine  officer  in  Puerto  Rico,  had 
been  sent  by  Surgeon  General  Wyman  to  continue  the  Service's  in- 
vestigation of  spotted  fever.  In  Puerto  Rico,  King  and  a  U.S.  Army 
physician,  Bailey  K.  Ashford,  had  demonstrated  that  a  severe  anemia 
found  on  the  island  was  caused  by  the  American  species  of  hookworm 
identified  by  Charles  Wardell  Stiles.  As  members  of  an  anemia  com- 
mission established  in  1904,  King  and  Ashford  had  worked  with  a 
Puerto  Rican  physician,  Pedro  Gutierrez,  to  develop  a  treatment  pro- 
gram that  reduced  the  death  rate  from  30  percent  to  less  than  i 
percent. 

Despite  King's  experience  in  public  health  work,  Ricketts  took  con- 
trol and  directed  the  experimental  work  from  the  outset.  King  noted 
that  Ricketts's  "education  for  the  work  was  very  thorough,"  and  that 


Dr.  Ricketts's  Discoveries 


53 


he  "looked  at  things  in  a  big  way,"  always  going  "straight  to  the  grist 
of  the  matter." Ricketts's  ability  to  conceptualize  experiments  that 
others  could  not,  or  had  not,  perhaps  best  reflects  the  impact  of  his 
training  with  leading  European  bacteriologists,  for  the  actual  tech- 
niques available  to  researchers  were  at  that  time  quite  simple.  Pure 
strains  of  bacteria  were  obtained  by  culturing  them  on  solid  gelatin 
media.  Experimental  animals  provided  a  means  to  isolate  pathogenic 
bacteria  from  a  sick  animal  as  well  as  to  show  that  a  bacterial  culture 
would  produce  a  particular  disease.  In  order  to  see  microorganisms 
under  the  microscope— itself  an  indispensible  bacteriological  tool— 
common  dyes  and  special  stains  were  used  on  blood  and  tissue  smeared 
on  glass  slides. 

A  rudimentary  knowledge  of  biochemical  reactions  faciHtated  the 
physiological  study  of  bacterial  metabolism,  and  theories  of  immunity 
informed  attempts  to  produce  vaccines,  antisera,  and  diagnostic  tests. 
The  agglutination  test,  for  example,  was  generally  considered  a  reliable 
indicator  of  the  presence  of  particular  disease  organisms.  Blood  was 
typically  drawn  from  a  person  recently  recovered  from  a  disease,  and 
a  procedure  known  as  defibrination  was  employed  to  speed  clotting. 
After  the  clot  was  removed,  the  blood  was  centrifuged  to  separate  the 
solid  cells  from  the  liquid.  To  the  serum  were  added  organisms  sus- 
pected of  causing  the  disease.  The  serum  of  the  recovered  patient 
contained  antibodies,  proteins  produced  by  the  body  in  response  to 
the  presence  of  foreign  proteins,  or  antigens.  Since  antibodies  bind  to 
their  complementary  antigens,  the  serum  would  clump  or  agglutinate 
if  the  patient  had  suffered  from  the  disease  caused  by  the  suspect 
organisms.  Although  exceptions  were  possible,  such  a  reaction  pro- 
vided strong  evidence  for  the  presence  of  the  disease  under  suspicion. 

Skilled  in  such  methods,  Ricketts  had  already  begun  a  microscopic 
study  and  culture  experiments,  and  he  was  outlining  future  experiments 
by  the  time  King  arrived.  Since  Ricketts  could  find  neither  Piroplasma 
nor  bacteria  in  the  blood,  and  King's  independent  study  confirmed 
that  none  was  present,  it  seemed  clear  that  the  spotted  fever  organism 
was  of  a  type  that  could  be  studied  only  in  an  experimental  animal. 
Both  Ricketts  and  King  thus  turned  their  energies  to  identifying  an 
animal  in  which  the  disease  could  be  easily  recognized.  Ricketts  first 
attempted  to  inoculate  rabbits  with  infected  blood,  but  the  results  were 
inconclusive,  two  animals  showing  no  signs  of  illness  and  a  third  only 
a  slight  fever.  If  readily  available  rabbits  were  unacceptable  models, 
funds  would  be  needed  to  purchase  other  laboratory  animals  until  a 
good  model  was  identified.  To  this  end,  E.  W.  Spottswood  addressed 
the  Missoula  Chamber  of  Commerce  on  1 5  May,  and  nine  days  later 


54 


Rocky  Mountain  Spotted  Fever 


the  Missoula  County  commissioners  appropriated  one  hundred  dollars 
to  fund  the  purchases.  The  Montana  State  Board  of  Health  secretary, 
Thomas  D.  Tuttle,  contributed  an  additional  forty  dollars  from  the 
board's  appropriation.^^ 

Ricketts  and  King  worked  independently,  but  they  shared  the  small 
amount  of  blood  available  from  spotted  fever  victims  as  they  inoculated 
guinea  pigs,  monkeys,  w^hite  rats,  and  mice  purchased  with  the  ap- 
propriated funds.  Since  the  most  favorable  route  for  inoculation  was 
unknown,  the  two  men  drew  lots  for  subcutaneous  and  intraperitoneal 
injections.  As  it  happened,  both  routes  proved  successful.  Only  the 
guinea  pigs  and  monkeys,  however,  displayed  a  definitive  feverish,  or 
febrile,  reaction.  The  less  expensive  guinea  pig  proved  an  ideal  model 
of  the  disease  in  humans.  It  ran  a  marked  fever,  and  the  males  displayed 
a  swollen  scrotum  that  became  a  characteristic  sign  of  spotted  fever 
infection.  When  Ricketts  attempted  to  maintain  the  disease  in  guinea 
pigs,  however,  he  had  difficulty,  but  he  was  able  to  sustain  the  infection 
in  animals  by  alternating  injections  in  monkeys  and  guinea  pigs.  This 
achievement  had  far-reaching  implications.  It  meant  that  he  could  study 
the  disease  year  round,  making  research  independent  of  the  incidence 
of  spotted  fever  cases.  Identifying  an  acceptable,  inexpensive  experi- 
mental animal  was,  in  Ricketts's  evaluation,  the  most  important  work 
accomplished  that  spring. 

Once  the  reaction  of  guinea  pigs  was  known  to  be  a  reliable  indicator 
that  the  disease  was  present,  Ricketts  conducted  experiments  to  de- 
termine whether  the  infectious  agent  was  a  microbe  or  a  toxin  and 
whether  it  was  confined  to  the  red  blood  cells  of  victims  or  was  trans- 
mitted also  by  the  serum  of  the  blood.  Short  on  blood  from  spotted 
fever  victims,  Ricketts  discovered  by  chance  on  ii  June  that  a  nine- 
year-old  girl,  Etta  Bradley,  was  severely  ill  with  the  disease  near 
Stevensville.^^  From  her  he  obtained  60-70  cc  of  blood,  some  of  which 
he  centrifuged  to  separate  the  heavier  red  and  white  cells  from  the 
hghter  serum.  The  solid  cells  were  washed  to  remove  any  remaining 
serum,  and  samples  of  the  serum  and  washed  cells  were  injected  into 
guinea  pigs.  Some  of  the  serum,  moreover,  was  passed  through  a 
ceramic  Berkefield  filter  at  low  pressure.  The  small  pores  of  such  filters 
obstructed  the  passage  of  most  microorganisms,  but  toxins  and  so- 
called  filterable  viruses  passed  through  unimpeded.  This  filtered  serum 
was  also  injected  into  a  guinea  pig. 

All  the  guinea  pigs  suffered  a  fatal  infection  except  for  the  one 
injected  with  filtered  serum.  This  indicated  that  the  infectious  agent 
was  not  a  toxin  or  filterable  virus  and  that  the  microbe  trapped  by 
the  filter  should  be  large  enough  to  be  seen  under  a  microscope.  In 


Dr.  Ricketts's  Discoveries 


55 


addition,  the  infectiveness  of  both  blood  corpuscles  and  unfiltered 
serum  demonstrated  that  the  spotted  fever  microbe  was  not  localized 
in  one  part  of  the  body,  as  was  true  in  tetanus,  but  rather  circulated 
in  the  blood.  The  finding  that  serum  was  infective  threw  further  doubt 
on  Wilson  and  Chowning's  Firoplasma  theory,  because  those  or- 
ganisms were  found  almost  exclusively  in  red  blood  cells. 

Ricketts  sent  a  manuscript  describing  these  experiments  to  the  Jour- 
nal of  the  American  Medical  Association^  which  published  it  in  the 
issue  of  7  July.  Although  these  preliminary  experiments  were  vital  in 
making  further  work  possible,  they  did  not  yet  answer  the  question 
burning  in  everyone's  mind:  Was  this  spotted  fever  microbe  transmitted 
by  the  bite  of  a  tick?  Both  Ricketts  and  King  began  tick  transmission 
experiments  just  as  their  stay  in  Montana  ended.  They  fed  ticks  on 
infected  guinea  pigs  and  placed  them  on  healthy  guinea  pigs.  Both 
researchers  got  positive  results  from  their  experiments— thus  dem- 
onstrating for  the  first  time  that  a  human  disease  in  the  United  States 
could  be  transmitted  by  a  tick.  After  returning  to  their  laboratories  in 
Chicago  and  Washington,  Ricketts  and  King  prepared  papers  on  the 
experiment.  King's  paper,  "Experimental  Transmission  of  Rocky 
Mountain  Spotted  Fever  by  Means  of  the  Tick,"  however,  was  pub- 
lished in  the  Public  Health  Reports  eight  days  before  Ricketts's  paper 
on  the  subject  appeared  in  the  Journal  of  the  American  Medical  As- 
sociation.^^ 

Having  spent  a  good  deal  of  his  own  money  to  finance  the  research 
as  well  as  having  conceived  the  experiment,  Ricketts  was  annoyed  at 
King's  priority  in  pubHshing  on  this  important  question.  "In  view  of 
the  result  which  I  had  obtained,"  Ricketts  wrote  in  his  article,  "I  was 
not  surprised  to  note  the  recent  report  of  Dr.  King,  .  .  .  who,  starting 
with  material  which  I  had  given  him,  accomplished  transmission  in 
the  same  manner."^^  Ricketts  had  already  complained  to  the  secretary 
of  the  Montana  State  Board  of  Health,  Thomas  D.  Tuttle,  about  the 
necessity  of  several  researchers  sharing  the  limited  quantity  of  available 
spotted  fever  blood.  Admitting  that  it  was  "a  little  bit  selfish  on  my 
part,"  Ricketts  requested  Tuttle  to  "Hmit  the  number  of  workers"  on 
spotted  fever  in  the  Bitterroot  the  following  season,  a  plea  Tuttle  had 
no  power  to  enforce.^^  The  incident  with  King  caused  Ricketts  to 
exercise  much  more  caution  in  sharing  material  or  reveaHng  the  results 
of  his  research  before  publication.^^ 

The  results  of  the  1906  work  infused  new  life  into  spotted  fever 
investigations.  In  the  same  issue  that  announced  the  enactment  of  the 
first  federal  pure  food  and  drugs  law,  the  journal  of  the  American 
Medical  Association  commented  editorially  that  Ricketts's  and  King's 


56 


Rocky  Mountain  Spotted  Fever 


"extremely  interesting  and  important  work"  would  provide  "a  new 
impetus"  to  spotted  fever  research.  Reflecting  prevailing  assumptions 
about  arthropods  and  the  types  of  organisms  they  might  transmit,  the 
editorial  also  observed  that  further  experiments  were  necessary  "to 
determine  whether  the  infecting  organism  must  undergo  a  cycle  of 
development,  as  in  the  case  with  some  organisms,  notably  the  Plas- 
modium malariae.'''^'^ 

The  secretary  of  the  Montana  State  Board  of  Health  was  jubilant 
over  Ricketts's  discoveries  but  dismayed  that  the  state  legislature  had 
not  supported  the  undertaking  financially.  In  his  summary  of  the  1906 
work.  Turtle  remarked  sarcastically  that  the  "magnanimous"  contri- 
bution of  the  state  toward  the  purchase  of  experimental  monkeys 
amounted  to  "the  extravagant  expenditure  of  forty  dollars."  To  con- 
tinue the  work  properly,  he  stated,  the  legislature  should  appropriate 
not  less  than  fifteen  hundred  dollars,  and  preferably  two  thousand 
dollars.  Ricketts  had  also  urged  the  state  to  appoint  a  legislative  study 
committee  and  to  appropriate  sufficient  money  to  continue  the  inves- 
tigation when  he  spoke  in  May  1906  at  the  Montana  Medical  Asso- 
ciation.^^ 

In  his  annual  report,  moreover,  Tuttle  broadened  his  crusade  for 
increased  funding  to  public  health  in  general.  He  noted  that  the  $2,000 
budget  of  the  state  board  of  health  was  paltry  compared  to  the  generous 
increases  given  to  other  state  boards— Massachusetts,  for  example, 
expended  $96,500  per  year;  Minnesota,  $20,000  per  year;  and  even 
scantily  populated  Colorado,  $5,000  per  year.  Raising  the  question  of 
whether  the  legislature  considered  the  life  of  a  Montanan  to  be  worth 
as  much  as  that  of  a  Bostonian,  Tuttle  challenged  the  lawmakers  to 
increase  funding  for  all  public  health  measures,  including  spotted  fever 
research.  This  emotional  appeal  apparently  swayed  state  legislators, 
because  they  appropriated  $2,000  for  further  work  by  Ricketts  during 
1907.^^ 

The  additional  funds  were  certainly  welcome,  because  the  work  of 
1906  opened  a  promising  new  direction  for  spotted  fever  investigations 
that  would  require  much  additional  research  before  the  disease  could 
be  prevented  or  treated.  The  tick  transmission  experiments  had  to  be 
repeated,  since  Ricketts  and  King  had  infected  only  a  single  guinea  pig 
each.  Furthermore,  proof  that  the  tick  could  transmit  the  disease  in 
the  laboratory  did  not  demonstrate  that  infected  ticks  existed  in  nature. 
If  such  ticks  did  exist,  virtually  nothing  was  known  about  their  life 
cycle  or  about  the  hosts  from  which  they  might  contract  the  infection. 
In  addition,  although  Ricketts  had  postulated  that  a  visible  microbe 


Dr.  Ricketts's  Discoveries 


57 


might  cause  the  disease,  no  one  had  yet  been  able  to  locate  it  under 
the  microscope  or  culture  it  in  the  laboratory.^' 

During  the  fall  and  wmter  of  1906-7,  King  and  Ricketts  continued 
their  research  on  spotted  fever  in  Washington  and  in  Chicago.  To 
enable  their  experiments  to  go  forward,  both  needed  a  continuous 
supply  of  ticks.  Each  wrote  to  contacts  in  the  Bitterroot,  who  enlisted 
local  newspapers  to  advertise  for  people  to  collect  ticks.  Locating  ticks 
after  they  disappeared  in  mid  summer,  however,  was  an  almost  im- 
possible task.  The  Western  Neivs,  believing  that  it  was  "worth  some- 
thing" to  discover  "where  the  ticks  are  in  the  winter,"  offered  ten 
dollars  in  gold  to  the  first  person  bringing  "50  or  more  live,  able- 
bodied  ticks"  to  the  newspaper  office  between  29  November  and  15 
December  1906.  Even  with  this  financial  incentive,  local  tick  sleuths 
were  apparently  baffled.  No  report  announced  that  the  gold  had  been 
claimed,  and  in  mid  December  the  paper  advertised  for  ticks  again, 
offering  "two  bits  per  head"  for  any  number  of  able-bodied  ticks,^^ 

With  the  few  ticks  he  was  able  to  obtain,  Ricketts  continued  his 
experiments  in  Chicago,  where  he  was  promoted  to  assistant  professor 
in  the  Department  of  Pathology-  and  Bacteriolog)^^^  Using  a  wire  mesh 
collar  he  had  designed  to  hold  ticks  in  place  on  the  guinea  pigs,  Ricketts 
conducted  experiments  to  demonstrate  that  male  as  well  as  female 
ticks  could  transmit  the  disease.  He  had  also  hoped  to  settle  the  question 
of  whether  female  ticks  transmitted  the  spotted  fever  organism  to  their 
offspring.  Unfortunately,  the  ticks  failed  to  breed,  so  the  experiment 
was  postponed  until  the  following  spring.  One  major  success  crowned 
Ricketts's  efforts  during  the  cold  Chicago  winter:  he  solved  the  problem 
of  how  to  preserve  the  spotted  fever  strain  in  guinea  pigs  alone.  He 
had,  of  course,  already  managed  to  maintain  the  infection  by  alter- 
nating inoculations  between  guinea  pigs  and  monkeys,  but  monkeys 
were  expensive.  In  his  first  attempts  with  guinea  pigs,  Ricketts  had 
taken  blood  from  a  dead  or  dying  pig  and  inoculated  it  into  a  fresh 
one.  The  infectious  agent,  he  discovered  by  repeated  experiments,  was 
most  virulent  during  the  height  of  the  disease.  With  this  information 
he  was  able  to  perpetuate  the  infection  in  guinea  pigs  alone  by  utilizing 
blood  from  a  sick  but  not  moribund  guinea  pig.^° 

Ricketts  began  the  new  season's  work  with  the  strain  of  spotted 
fever  he  had  successfully  sustained  in  guinea  pigs.  This  proved  for- 
tunate, for  spotted  fever  cases  occurred  only  sporadically,  and  the 
famihes  of  victims  did  not  always  welcome  a  doctor  whose  primary 
interest  was  research.  In  1907  the  first  case  of  spotted  fever  did  not 
appear  until  mid  April.  It  struck  a  twent>'-six-year-old  lumberman, 


58 


Rocky  Mountain  Spotted  Fever 


Maurice  J.  Holden,  who  was  secretary-treasurer  at  the  Florence  lodge 
of  the  International  Workmen  of  the  World.  Ricketts  visited  the  patient, 
but  Holden's  family  "objected  to  a  thorough  examination"  and  refused 
to  allow  Ricketts  to  draw  any  blood.  When  Ricketts  apprised  Turtle 
of  this  situation,  the  secretary  of  the  state  board  of  health  prepared 
an  official-looking  document  instructing  local  people  to  cooperate  with 
the  investigation.  He  admonished  Ricketts,  however,  not  to  present 
the  document  "where  people  are  liable  to  look  into  it  too  closely," 
because  in  truth  "we  have  no  authority"  to  issue  it.^^ 

Walter  W.  King  also  returned  to  the  Bitterroot  in  the  spring  of  1907, 
as  did  William  M.  Chowning,  who  continued  to  study  the  variety  of 
organisms  he  found  in  spotted  fever  blood. Ricketts  and  King  resumed 
their  studies,  jointly  visiting  cases  and  drawing  blood.  Wary  of  King's 
competition,  however,  Ricketts  conducted  his  experiments  alone. 
"King  and  I  have  had  no  difficulty  so  far,"  Ricketts  wrote  to  Ludvig 
Hektoen,  but  he  characterized  King  as  having  "many  questions  to  ask 
in  his  smooth  'governmental'  fashion. "^^ 

Ricketts  worked  intensely  on  the  question  of  whether  female  ticks 
could  transmit  spotted  fever  to  their  offspring.  He  worried  that  King 
might  again  publish  first  on  this  important  question.  In  a  letter  to 
Hektoen,  Ricketts  noted  that  King  had  "sent  ripened  females  to  Wash- 
ington," where  "doubtless"  King's  colleagues  would  soon  be  "at  work 
on  these  points."  Ricketts's  assistants  also  collected  ticks  from  known 
spotted  fever  locales  for  experiments  to  determine  if  infected  ticks 
existed  in  nature.  Describing  this  work  to  Hektoen  as  the  most  im- 
portant of  all,  Ricketts  emphasized  that  this  experiment  in  particular 
was  the  one  he  wanted  "to  get  into  print  as  soon  as  possible."  Although 
King  appeared  to  be  conducting  only  small-scale  research  on  this  prob- 
lem, Ricketts  feared  that  it  might  be  "just  his  luck"  for  King  to  get 
the  answer  first.^'* 

For  all  Ricketts's  foreboding,  however.  King's  1907  work  resulted 
in  no  publications,  and  shortly  after  King  returned  to  Washington, 
D.C.,  he  was  detached  from  the  Hygienic  Laboratory  and  ordered  to 
San  Francisco  for  duty.  Since  the  laboratory  director,  Milton  J.  Ro- 
senau,  retained  only  the  Service's  most  promising  research  scientists 
on  his  staff,  it  is  possible  that  King's  failure  at  least  to  match  Ricketts's 
achievements  indicated  to  Rosenau  that  King  was  more  suited  for  other 
types  of  work.  After  leaving  spotted  fever  investigations.  King  returned 
to  his  work  as  a  quarantine  officer,  serving  at  San  Francisco,  Ellis 
Island,  and  Naples,  Italy.^^ 

After  the  1907  spotted  fever  season,  Ricketts  had  the  field  virtually 
to  himself.  His  research  was  conducted  on  a  variety  of  fronts,  including 


Dr.  Ricketts's  Discoveries 


59 


efforts  to  identif)^  the  spotted  fever  organism  and  experiments  with  a 
potential  antiserum  and  a  vaccine  against  spotted  fever.  Reahzing  that 
effective  therapeutic  measures  might  take  a  number  of  years  to  develop, 
Ricketts  devoted  much  of  his  time  in  1907  and  1908  to  understanding 
the  relationship  between  spotted  fever  and  the  tick.  Such  knowledge, 
he  hoped,  would  provide  the  basis  for  developing  a  practical  program 
for  controlling  the  tick,  thereby  reducing  the  incidence  of  the  disease. 

The  question  of  possible  hereditary  transmission  of  the  spotted  fever 
organism  was  of  vital  importance.  With  the  assistance  of  two  students, 
Paul  G.  Heinemann  and  Josiah  J.  Moore,  Ricketts  devised  an  exper- 
iment in  which  sixty  female  ticks  were  fed  on  infected  guinea  pigs  and 
then  allowed  to  breed.  Of  these,  twenty-six  produced  eggs.  The  larvae 
produced  by  each  female  were  then  placed  on  a  healthy  guinea  pig  to 
see  if  spotted  fever  had  been  transmitted  to  them  by  their  mothers. 
The  results  of  this  tedious  process,  which  required  meticulous  handling 
and  record-keeping  at  each  stage,  were  somewhat  surprising.  Of  the 
twenty-six  groups  of  larvae,  only  two  infected  the  guinea  pigs  on  which 
they  fed.  "If  this  was  the  result  in  twenty-six  laboratory  experiments," 
Ricketts  wrote,  "it  is  fair  to  conclude  that .  .  .  only  a  small  percentage 
of  infected  females  passes  the  disease  on  to  their  young"  in  nature. 
When  Ricketts  and  his  part-time  colleague  Maria  B.  Maver  repeated 
these  experiments,  they  achieved  somewhat  higher  percentages  of 
transmission.^^  The  results  were  clear,  however:  hereditary  transmis- 
sion did  occur,  but  only  in  a  minority  of  cases.  This  finding,  coupled 
with  additional  research  that  showed  the  salivary  glands  of  the  tick 
also  to  be  infective,  led  Ricketts  to  conclude  that  spotted  fever  was 
probably  a  generahzed  infection  of  tick  tissues  that  was  transmitted 
biologically  by  the  tick  through  biting.^" 

Determining  whether  infected  ticks  existed  in  nature— the  work  that 
Ricketts  had  been  so  anxious  to  publish— was  likewise  a  tedious  pro- 
cess. Each  year  from  1907  to  1909,  Ricketts  collected  ticks  and  watched 
to  see  if  any  guinea  pigs  on  which  they  fed  became  ill.  As  in  the 
hereditary  experiments,  Ricketts  found  that  only  a  small  number  of 
ticks  contained  the  virulent  organism,  because  most  of  the  guinea  pigs 
remamed  healthy.  Convinced  at  last  that  his  work  was  definitive,  Rick- 
etts wrote  to  Tuttle  that  three  years  of  experiments  should  be  "enough 
to  prove  to  the  satisfaction  of  everyone  that  infected  ticks  do  occur 
naturally"  but  in  small  numbers. 

Having  determined  that  the  Rocky  Mountain  wood  tick  carried 
spotted  fever,  Ricketts  assigned  Maver  the  task  of  determining  whether 
other  ticks  could  carry  the  infection  as  well.  Initially,  Maver  dem- 
onstrated that  the  tick  carrying  the  mild  Idaho  spotted  fever  could 


6o 


Rocky  Mountain  Spotted  Fever 


also  transmit  the  virulent  Bitterroot  Valley  strain  and,  conversely,  that 
the  tick  found  in  the  Bitterroot  could  transmit  the  mild  Idaho  strain 
of  the  disease.  During  the  summer  and  fall  of  1909,  Maver  began 
experiments  with  the  dog  tick  common  to  the  eastern  United  States, 
the  "lone  star"  tick  common  on  cattle  from  Missouri  to  Texas  and 
Louisiana,  and  a  rabbit  tick  from  Utah.  All  three  ticks  transmitted 
spotted  fever  to  guinea  pigs.  "From  these  experiments,"  Maver  w^rote, 
"it  appears  that  .  .  .  the  disease  might  find  favorable  conditions  for 
its  existence  in  localities  other  than  those  to  which  it  now  is  limited." 
At  this  time  there  was  concern  that  spotted  fever  might  spread  within 
the  western  United  States  but  no  indication  that  it  might  exist  in  other 
parts  of  North  America. 

The  life  cycle  of  the  Rocky  Mountain  wood  tick  was  another  problem 
to  be  solved  before  tick  control  could  be  implemented.  From  his  brief 
observations  over  a  single  year,  Ricketts  provided  an  initial  description 
of  how  ticks  reproduced.  After  fertilization,  which  occurred  on  large 
host  animals  such  as  cattle  and  horses: 

the  female  continues  to  feed  for  several  days  .  .  .  and  during  this  time  enlarges 
very  rapidly,  until  she  is  finally  transformed  into  the  large  gray  or  slate  colored 
tick.  On  the  other  hand,  the  male,  after  prolonged  feeding,  undergoes  no  more 
enlargement  than  would  be  caused  by  the  distension  of  a  good  feed.  The 
enlargement  of  the  female  is  due  partly  to  the  quantity  of  blood  it  has  ingested, 
but,  in  addition,  the  change  is  to  be  looked  on  as  sexual.  The  ovaries  become 
greatly  developed  and  hundreds  or  even  thousands  of  minute  eggs  begin  their 
rather  slow  formation. 

When  the  female  has  reached  its  greatest  degree  of  enlargement,  it  drops 
from  the  animal  and,  after  a  rest  of  about  two  weeks  or  longer  in  cold  weather, 
begins  to  lay  eggs.  The  eggs  are  withdrawn  from  the  anterior  end  of  the  lower 
surface  of  the  body,  the  head  parts  assisting  in  their  extrusion,  and  they 
accumulate  in  small  masses  on  the  back  of  the  head.  As  their  bulk  becomes 
heavy  they  fall  off  and  are  replaced  gradually  by  a  second  mass.  This  process 
continues  until  all  the  eggs,  which  may  number  several  hundred  or  even  two 
or  three  thousand,  lie  in  a  heap  before  the  tick.  In  the  meantime  the  female 
becomes  greatly  flattened  and  wrinkled  and,  in  a  comparatively  short  time 
dies.  A  female  which  has  laid  eggs  never  again  assumes  the  appearance  of  the 
young  red  female  and  her  life  is  ended  in  one  season. 

The  newly  hatched  six-legged  larvae,  Ricketts  believed,  fed  on  small 
animals,  molted  into  eight-legged  nymphs,  and  fed  again.  The  nymphs 
then  molted  into  sexually  mature  adults.  Ricketts  could  not  determine 
precisely  how  long  this  process  took  but  noted  that  it  was  possible  to 
speed  it  up  in  the  laboratory  by  using  incubators  and  providing  im- 
mediately available  hosts  for  each  stage.  He  believed,  however,  that 
eggs  deposited  one  year  became  adults  capable  of  reproducing  during 
the  following  spring."^^ 


Dr.  Ricketts's  Discoveries 


6i 


Working  from  an  assumed  twelve-month  life  cycle,  which  later 
would  be  shown  to  be  incorrect,  Ricketts  attempted  to  formulate  a 
program  for  control  of  the  tick.  Other  arthropod-borne  diseases  that 
served  as  models  for  this  effort  were  malaria,  yellow  fever,  and  Texas 
cattle  fever.  Yellow  fever  control  efforts  had  clearly  demonstrated  that 
the  Anopheles  mosquito  needed  only  to  be  reduced  to  a  certain  level 
to  control  the  disease;  it  did  not  have  to  be  eHminated."^^  Since  Ricketts 
had  already  demonstrated  that  the  percentage  of  ticks  in  nature  infected 
with  spotted  fever  was  small,  diminishing  the  total  tick  population 
promised  a  significant  reduction  in  spotted  fever  cases. 

One  key  intervention  strategy  was  preventing  adult  ticks  from  reach- 
ing the  large  animals  on  which  they  fed  and  mated.  If  this  could  be 
accompHshed,  subsequent  generations  of  ticks  would  never  be  born. 
The  Texas  cattle  fever  tick  had  been  virtually  eliminated  by  this  method. 
Because  that  tick  remained  through  its  entire  life  cycle  on  a  single 
animal,  it  had  been  possible  to  create  tick-free  pastures  simply  by 
removing  stock.  Ticks  remaining  on  the  ground  starved  for  lack  of  a 
host.  Once  a  pasture  had  been  purged  of  ticks,  stock  from  which  all 
ticks  had  been  carefully  removed  could  be  safely  returned.  A  few  years 
of  alternating  pastures  in  this  manner  effectively  eliminated  the  Texas 
cattle  fever  menace.  A  second  approach  to  tick  control  consisted  of 
oiling  the  bodies  of  stock  by  hand  or  by  dipping  them  in  large  vats 
several  times  during  tick  season.  Oil  was  repugnant  to  ticks,  repelling 
unattached  ticks  and  causing  those  already  attached  to  lose  their  hold. 
According  to  the  Bureau  of  Animal  Industry,  moreover,  oiling  pro- 
duced no  permanent  injury  to  the  cattle  and  horses. 

Ricketts  corresponded  about  these  methods  with  an  entomologist 
at  the  University  of  Tennessee  Agricultural  Experiment  Station,  H.  A. 
Morgan,  who  had  a  great  deal  of  experience  in  the  control  of  Texas 
cattle  fever.  Because  the  spotted  fever  tick  had  different  hosts  at  each 
stage  of  its  life  cycle,  Morgan  doubted  that  alternating  pasturage  would 
be  effective.  In  his  report  to  the  Montana  State  Board  of  Health, 
therefore,  Ricketts  recommended  that  the  state  undertake  a  program 
of  oiling  to  reduce  the  tick  population  in  settled  areas.  "Total  exter- 
mination of  the  tick  cannot  be  promised  or  expected,"  Ricketts  wrote, 
since  wild  animals  in  the  mountains  would  continue  to  act  as  hosts. 
"But  this  does  not  mean  that  the  territory  inhabited  by  the  residents 
must  continue  to  be  infested  with  ticks. '"^'^ 

These  preliminary  recommendations,  which  included  the  admoni- 
tion that  citizens  also  rid  their  premises  of  the  ground  squirrels  that 
served  as  hosts  to  immature  states  of  the  tick,  were  based  on  the  scanty 
information  about  the  life  cycle  of  the  tick  that  Ricketts  was  able  to 


62 


Rocky  Mountain  Spotted  Fever 


gain  in  a  few  months'  time.  He  advised  that  additional  observations 
should  be  carried  out  year  round,  and  he  recommended  entomologists 
M.  J.  Elrod  of  the  University  of  Montana  and  Robert  A.  Cooley  of 
the  Montana  State  College  as  potential  candidates. In  1908,  Cooley, 
w^hose  work  will  be  discussed  in  chapter  5,  took  up  the  study. 

The  first  of  two  reports  Ricketts  prepared  was  written  in  a  popular 
style  and  widely  disseminated  because  many  people  in  the  Bitterroot 
continued  to  doubt  the  tick  theory  of  spotted  fever  transmission.  "It 
is  absolutely  necessary,"  Ricketts  noted,  for  Bitterroot  residents  "to 
know  something  about  the  life  history  of  the  tick  and  its  bearing  on 
the  question  if  they  are  to  accept  the  tick  theory.'"^^  Thus,  in  addition 
to  his  formal  recommendations,  Ricketts  included  practical  informa- 
tion on  dealing  with  tick  bites.  Countering  superstitions  about  how 
one  must  approach  an  attached  tick,  Ricketts  stated:  "The  tick,  if 
attached,  should  be  removed  immediately,  not  by  attempting  to  'un- 
screw' it  as  is  so  often  recommended,  but  by  grasping  the  body  firmly 
and  pulling  gently  and  continuously.  ...  A  sudden  jerk  is  likely  to 
tear  the  body  from  the  head,  leaving  the  latter  imbedded  in  the  skin. 
A  drop  of  kerosene  oil  will  cause  the  animal  to  loosen  its  hold.'"^^ 

He  also  advised  those  bitten  not  to  apply  carboHc  acid  with  the 
stopper  of  the  bottle  or  by  inverting  the  bottle  over  the  wound.  Such 
a  procedure,  Ricketts  warned,  was  "both  inefficient  and  dangerous" 
because  it  burned  an  excessive  area  of  the  skin.  The  actual  point  at 
which  the  tick  inserted  its  fine  toothed  proboscis  into  the  skin  and 
deposited  the  spotted  fever  organisms  was  small.  "The  proper  method 
of  applying  the  carbolic  acid,"  therefore,  was  "to  dip  a  sharp  pointed 
toothpick  or  splinter  of  wood  into  the  acid  .  .  .  and  then  to  thrust  the 
tip  deeply  into  the  point  of  the  bite,  twisting  the  wood  as  it  penetrates." 
The  first  application  was  rather  painful,  Ricketts  admitted,  but  the 
acid  had  a  tendency  to  destroy  the  sense  of  pain,  and  the  second  and 
third  applications  immediately  following  would  cause  only  "a  small 
degree  of  discomfort.'"^^ 

Even  this  recommended  method,  however,  carried  no  guarantee 
since,  as  Ricketts  observed,  "we  have,  as  yet,  no  experimental  evidence 
to  show  just  how  effective  cauterization  of  the  tick  wound  with  carbolic 
acid  is  in  preventing  spotted  fever."  He  doubted  that  any  treatment 
was  effective  if  the  tick  remained  attached  for  several  hours.  "The 
virus  in  a  short  time  probably  extends  too  far  for  the  acid  to  have  any 
effect  on  it,"  he  stated.  Later  experiments  by  his  student,  Josiah  J. 
Moore,  indeed  demonstrated  that  within  two  hours,  an  attached  tick 
could  inject  enough  spotted  fever  organisms  to  cause  the  disease."*^ 

Opinion  remained  divided  in  the  Bitterroot  about  the  tick  theory, 


Dr.  Ricketts's  Discoveries 


63 


but  businessmen  supported  Ricketts  and  hoped  his  findings  could  be 
used  to  stabihze  land  prices.  In  June  1907  a  "woodtick  dance"  at 
Florence  raised  funds  for  burning  brush  in  which  ticks  were  plentiful. 
Real  estate  salesmen  promoting  sweet  and  sour  cherries  as  well  as 
apples  to  Chicago  clients  sought  to  minimize  the  impact  of  spotted 
fever  on  land  sales  with  tangible  proof  that  the  entire  valley  was  not 
affected.  A  representative  of  the  Bitter  Root  Valley  Irrigation  Company 
asked  Tuttle,  the  secretary  of  the  state  board  of  health,  if  he  and  Ricketts 
would  prepare  a  joint  statement  that  the  west  side  of  the  valley  alone 
was  infected.  The  company  planned  to  publish  this  document  "for  the 
purpose  of  furthering  the  sales  of  land."  Ricketts  and  Tuttle  complied, 
with  the  stipulation  that  their  names  be  used  "with  due  modesty  and 
discretion. "^° 

Although  his  plan  to  control  ticks  was  of  paramount  importance, 
Ricketts  also  pressed  forward  in  a  number  of  other  areas.  One  was 
identifying  the  elusive  spotted  fever  organism.  From  the  beginning  of 
his  work,  Ricketts  had  tried  to  culture  a  bacterium  with  no  success, 
although  his  filtration  experiments  had  convinced  him  that  the  germ 
must  be  large  enough  to  see  with  a  microscope.  He  tried  various  staining 
methods,  including  the  Giemsa  and  Levaditi  stains,  considered  best 
for  reveahng  parasites  in  the  blood.  With  the  Giemsa  stain — the  world's 
standard  diagnostic  agent  for  malarial  organisms  — Ricketts  consist- 
ently found  "small  spherical,  ovoid  and  diplococcoid  forms,"  which 
seemed  to  be  bacteria.  To  prove  bacterial  causation  according  to  Koch's 
postulates,  however,  Ricketts  had  to  culture  the  organisms  on  artificial 
media.  Despite  repeated  attempts,  he  had  not  been  successful.^^ 

Ricketts  therefore  declined  to  publish  a  claim  that  the  diplococcoid 
bodies  were  the  cause  of  spotted  fever.  Prevailing  scientific  opinion, 
moreover,  continued  to  support  the  belief  that  arthropods  transmitted 
only  protozoan  organisms  biologically.  In  a  1908  article  reviewing  the 
state  of  knowledge  of  ticks  and  disease,  W.  A.  Hooker  of  the  U.S. 
Bureau  of  Entomology  outHned  the  piroplasmic  diseases  carried  by 
ticks.  Although  he  noted  that  the  spotted  fever  organism  remained 
unidentified.  Hooker's  evidence  lent  credence  to  the  hypothesis  that 
spotted  fever  would  probably  also  be  a  Piroplasma  or  Spirilla  — or- 
ganisms  known  to  be  transmitted  by  ticks.  Two  years  later,  Rennie 
W.  Doane,  an  assistant  professor  of  entomology  at  Leland  Stanford, 
Jr.,  University,  pubhshed  a  popular  book  entitled  Insects  and  Disease, 
in  which  he  argued  that,  among  parasitologists,  spotted  fever  was 
"quite  generally  believed"  to  be  carried  by  some  sort  of  protozoan 
organism. 

Nonetheless,  by  January  1909,  Ricketts  was  convinced  that  he  had 


64 


Rocky  Mountain  Spotted  Fever 


indeed  identified  the  spotted  fever  microbe.  His  published  description 
of  the  bacillus  was  conservatively  entitled  "A  Micro-Organism  Which 
Apparently  Has  a  Specific  Relationship  to  Rocky  Mountain  Spotted 
Fever:  A  Preliminary  Report."  He  characterized  the  organism  as  "a 
bipolar  staining  bacillus  of  minute  size,  approximating  that  of  the 
influenza  bacillus  [s/c],  although  definite  measurements  have  not  yet 
been  made."  Agglutination  experiments  w^ith  the  bacillus  in  tick  eggs 
produced  no  reaction  v^^ith  the  blood  of  normal  guinea  pigs,  but  the 
blood  of  immune  guinea  pigs  — those  w^hich  had  recovered  from  a  bout 
with  spotted  fever— produced  the  "striking  result"  of  complete  agglu- 
tination in  dilutions  of  up  to  i  to  320.  "In  so  far  as  I  know,"  Ricketts 
wrote,  "it  would  be  an  unheard-of  circumstance  to  obtain  such  strong 
agglutination  with  an  immune  serum,  in  the  presence  of  negative  con- 
trols, unless  there  were  a  specific  relationship  between  the  organism 
and  the  disease. "^^ 

Noting  that  he  had  employed  rehable  staining  methods  in  searching 
for  presumed  Piroplasma  or  Spirilla,  moreover,  Ricketts  argued  that 
the  organism  of  spotted  fever  showed  bacterial,  not  protozoan,  char- 
acteristics. In  addition,  he  reiterated  Charles  Wardell  Stiles's  clinical 
findings  that  clearly  differentiated  spotted  fever  from  the  piroplas- 
moses.^"^  "That  a  bacillus  may  be  the  causative  agent  of  a  disease  in 
which  an  insect  carrier  plays  an  obligate  role  under  natural  conditions 
may  be  looked  at  with  suspicion  in  some  quarters,"  he  observed, 
anticipating  the  reaction  his  preliminary  communication  might  bring. 
"Yet  ...  it  would  seem  to  be  unscientific,"  he  admonished  his  col- 
leagues, "to  be  tied  to  the  more  or  less  prevailing  belief  that  all  such 
diseases  must,  on  the  basis  of  several  analogies,  be  caused  by  parasites 
which  are  protozoon  in  character."^^ 

Ricketts  was  cautious  in  his  pubhshed  statements,  but  to  his  friends 
he  revealed  complete  assurance.  "Just  a  note  to  tell  you  that  I  have 
found  the  microorganism  of  spotted  fever,"  Ricketts  wrote  to  Tuttle 
just  before  the  JAMA  article  was  published.  "The  eggs  of  infected 
female  ticks  are  loaded  with  them,"  he  added,  describing  the  organism 
as  "similar  to  the  plague  bacillus"  but  smaller.  A  distinguished  Mich- 
igan bacteriologist,  F.  G.  Novy,  who  had  corresponded  with  Ricketts 
about  staining  techniques  during  his  research,  congratulated  Ricketts 
and  observed  that  the  tick-bacillus  connection,  if  proven,  would  over- 
turn existing  beliefs  about  arthropod  vectors:  "If  you  can  clinch  the 
story  it  will  be  a  fine  one  which  will  kind  of  upset  some  of  our  cock- 
sure friends."  WiUiam  M.  Chowning,  still  unforgiving  about  Stiles's 
ridicule  of  his  earlier  work,  was  "more  than  pleased"  that  Ricketts 


Dr.  Ricketts's  Discoveries 


65 


had  "placed  the  problem  where  Stiles  will  be  compelled  to  backwater 
again."^^ 

Feeling  certain  that  he  had  identified  the  spotted  fever  organism,  but 
also  knowing  that  scientific  proof  as  yet  eluded  him,  Ricketts  com- 
mented on  his  dilemma  to  Tuttle:  "I  remind  you  that  we  have  not  yet 
been  able  to  cultivate  [the  microbe],  and  thus  meet  one  of  Koch's  great 
laws.  This  makes  it  necessary  to  bring  all  kinds  of  indirect  evidence 
to  bear  showing  that  we  have  the  real  thing."  He  promised  Tuttle  that 
the  cultivation  work  would  be  continued  until  success  was  achieved 
"or  until  we  have  satisfied  ourselves  that  it  cannot  be  done."  Ricketts 
placed  much  of  the  responsibiHty  for  these  studies  on  Eugene  Franklin 
McCampbell,  a  professor  of  bacteriology  at  Ohio  State  University, 
who  in  1909  was  a  visiting  lecturer  at  the  University  of  Chicago. 
Interested  in  the  challenge  presented  by  this  stubborn  organism, 
McCampbell  seemed  to  make  headway  against  it;  in  November  he 
wrote  Ricketts  that  he  had  isolated  a  culture  of  the  small  diplobacillus 
that  corresponded  morphologically  "exactly  with  that  seen  in  the  tick 
eggs  and  in  the  blood."  It  was  so  virulent,  McCampbell  claimed,  that 
injections  of  water  condensation  in  the  culture  tubes  killed  guinea  pigs 
in  twenty-four  to  thirty-six  hours.  Unfortunately,  McCampbell  did  not 
describe  his  method,  nor  did  he  publish  his  results. 

Ricketts  also  utilized  his  specialized  knowledge  of  vaccines  and  se- 
rum therapy  in  attempts  to  produce  a  prophylactic  vaccine  and  a 
curative  serum.  As  early  as  1907  he  had  optimistically  commenced 
vaccination  experiments,  "a  la  Pasteur."  In  using  this  phrase,  Ricketts 
was  referring  to  Louis  Pasteur's  empirical  attenuation  of  the  rabies 
virus  by  drying  infected  spinal  cords  of  animals  over  a  period  of  time, 
for  no  one  had  isolated  the  rabies  pathogen  when  Pasteur  worked. 
Assisted  by  his  student  Liborio  Gomez,  Ricketts  similarly  endeavored 
to  attenuate  the  spotted  fever  organism.  They  desiccated  it  "over  sul- 
phuric acid"  and  planned  a  series  of  injections  that  would  use  increas- 
ingly "smaller  quantities  of  virus  which  had  been  dried  for  shorter 
periods,  passing  finally  to  minute  amounts  of  fresh  virus."^^  Unfor- 
tunately, this  method  did  not  work;  the  organisms  were  either  killed 
outright  or  remained  completely  infective. 

Having  determined  that  the  minimum  pathogenic  dose  of  blood 
infected  with  spotted  fever  was  between  0.0 1  and  0.03  cc  for  guinea 
pigs,  Ricketts  and  Gomez  next  attempted  to  produce  immunity  by 
allowing  animals  to  build  up  resistance  to  extremely  small  doses  of 
the  organism.  This  idea  was  also  quickly  abandoned.  "As  a  rule,"  they 
noted,  a  minute  quantity  [of  infected  blood]  either  produces  frank 


66 


Rocky  Mountain  Spotted  Fever 


infection  or  causes  no  disturbance  whatever.  .  .  .  On  account  of  the 
uncertainty  as  to  what  the  virus  will  do  when  injected  in  quantities 
which  approximate  the  minimum  pathogenic  dose,  it  is  manifest  that 
minute  doses  cannot  be  utihzed  for  practical  vaccination."^^ 

More  promising  experiments  resulted  from  mixing  small  quantities 
of  infected  blood  with  "immune"  blood  — that  is,  blood  from  an  animal 
that  had  recovered  from  spotted  fever.  Since  it  was  known  that  a  single 
infection  with  the  disease  produced  lasting  immunity— which  was  also 
passed  to  the  offspring  of  immune  females  — Ricketts  hypothesized  that 
the  immune  blood  would  neutralize  the  live  organisms  sufficiently  to 
prevent  a  fatal  case  of  the  disease  and,  at  the  same  time,  produce 
immunity  in  the  inoculated  animal.  Experiments  with  guinea  pigs  dem- 
onstrated that  this  "sero-vaccination"  was  efficacious.  Ricketts  was 
cautious,  however,  about  generalizing  the  findings  from  guinea  pigs 
to  humans.  Observing  that  "the  unknown  susceptibility  of  man  in 
comparison  with  that  of  the  monkey  and  guinea  pig"  was  a  serious 
stumbling  block  to  direct  application  of  the  technique  to  humans,  he 
suggested,  "Only  one  method  could  possibly  be  advocated  at  the  outset; 
namely,  to  use  such  proportions  of  virus  and  immune  serum  as  would 
leave  no  question  as  to  the  safety  of  the  procedure,  assuming  for  the 
time  that  the  virus  has  the  greatest  possible  virulence  for  man."^° 

Before  this  method  could  be  pursued  further,  Ricketts  made  a  dis- 
covery that  stimulated  a  completely  different  approach  toward  pro- 
ducing a  spotted  fever  vaccine.  While  examining  the  tissues  and  eggs 
of  noninfective  ticks  used  as  controls  in  his  experiments,  Ricketts  was 
astonished  to  find  that  many  contained  bacilli  morphologically  iden- 
tical to  the  virulent  organisms  in  infective  ticks.  These  bacilli,  moreover, 
would  also  agglutinate  immune  serum  but  not  normal  serum.  "I  have 
come  to  the  conclusion,"  he  stated,  "that  avirulent  strains  of  the  spotted 
fever  microbe  are  to  be  found  in  nature  in  the  tick."  He  realized,  of 
course,  that  this  point  must  be  proved  "in  order  to  have  the  microbe 
above  reproach  in  the  eyes  of  scientific  critics,"  but  he  also  viewed  the 
avirulent  organisms  as  potentially  the  "nucleus  of  a  successful  vac- 
cine."^i 

Ricketts  asked  Eugene  Franklin  McCampbell  to  conduct  experi- 
ments on  the  vaccinating  power  of  noninfective  tick  eggs.  A  shortage 
of  guinea  pigs  slowed  the  new  work  to  some  extent,  but  results  of 
initial  experiments  were  promising.  "We  have  a  few  experiments," 
Ricketts  wrote  to  Ludvig  Hektoen,  "which  indicate  that  vaccination 
takes  place  when  the  eggs  or  organs  of  ticks  which  contain  avirulent 
bacilli  are  injected  into  guinea  pigs."  Ricketts  hoped  to  bring  this  series 
of  experiments  to  a  conclusion  during  the  winter  of  1909—10.^^ 


Dr.  Ricketts's  Discoveries 


67 


At  the  same  time,  Ricketts  also  pursued  the  development  of  an 
antiserum  for  treating  those  already  ill  with  the  disease.  Elie  Metch- 
nikoff  had  pioneered  serum  therapy  by  producing  an  antitoxin  in  horses 
that  would  dramatically  halt  the  ravages  of  diphtheria.  Hoping  to 
produce  a  similarly  effective  product  for  spotted  fever,  Ricketts  began 
by  "hyperimmunizing"  a  small  group  of  guinea  pigs  and  horses. This 
was  accomplished  by  injecting  an  animal  that  had  recovered  from 
spotted  fever— and  thereby  had  achieved  immunity  to  it— with  addi- 
tional doses  of  the  organism.  Over  a  period  of  time,  the  animal's  blood 
built  up  massive  amounts  of  antibody  to  the  pathogen.  This  process 
rendered  the  animal  "hyperimmune"  and,  potentially,  made  its  serum 
valuable  as  a  treatment  against  an  active  case  of  the  disease. 

By  the  spring  of  1908,  Ricketts  had  produced  an  antiserum  that 
protected  guinea  pigs  against  spotted  fever  if  given  a  short  time  after 
infection.  It  was  impossible,  of  course,  to  judge  whether  it  would  have 
any  effect  on  humans,  especially  since  it  would  have  to  be  given  in 
relatively  large  amounts.  Moreover,  information  about  anaphylaxis  — 
the  life-threatening  allergic  response  that  struck  some  people  injected 
more  than  once  with  the  foreign  proteins  in  horse  serum— was  just 
becoming  widely  known.  Writing  to  Thomas  D.  Tuttle,  Ricketts  noted 
a  recently  published  article  in  the  Journal  of  the  American  Medical 
Association  dealing  with  anaphylaxis,  but  he  expressed  the  opinion 
that  large  doses  of  his  antiserum  would  carry  no  significant  risk.  "I 
have  known  over  1000  cc  of  horse  serum,  in  the  shape  of  tetanus 
antitoxin,  to  be  given  subcutaneously,  intravenously,  and  subdurally, 
without  producing  any  serious  damage. "^^ 

Because  of  the  high  mortality  from  spotted  fever  in  the  Bitterroot 
Valley,  Ricketts  concluded  that  it  would  do  no  harm  to  test  the  serum 
on  victims  of  the  disease.  During  the  spring  of  1908  he  administered 
the  serum  to  nine  spotted  fever  patients.  Six  of  them,  all  extremely  ill, 
died  in  spite  of  the  treatment.  In  each  of  the  three  recoveries,  there 
were  circumstances  that  threw  doubt  on  the  efficacy  of  the  serum.  The 
disease  was  exceptionally  mild  from  the  beginning  in  a  seven-year-old 
boy,  who  received  138  cc  of  the  serum,  and  in  one  adult  male,  whose 
physician  failed  to  keep  records  on  the  amount  of  serum  administered. 
In  the  case  of  the  child,  moreover,  it  was  widely  known  that  children 
were  more  likely  to  recover  than  adults.  A  more  typical  case  treated 
that  spring  occurred  in  an  adult  male,  who  received  120  cc  of  the 
serum  over  three  days.  Although  the  man  lived,  his  recovery  took  two 
weeks.  Ricketts  doubted  that  the  serum  caused  the  recovery,  observing 
that  "there  would  be  less  difficulty  in  recognizing  a  curative  effect  of 
the  serum  if  its  injection  were  followed  by  a  sudden  subsidence  of 


68 


Rocky  Mountain  Spotted  Fever 


symptoms,  such  as  antitoxin  causes  in  diphtheria. "^^ 

In  contrast  to  Ricketts's  own  conclusions,  the  local  press  judged  that 
the  serum  had  indeed  saved  the  victims'  lives. It  was  hardly  surprising 
that  the  relatives  of  spotted  fever  patients  grasped  at  the  promise  of 
the  serum  and  rarely  worried  about  its  proven  efficacy.  Because  of  this, 
Ricketts  received  numerous  appeals  in  the  spring  of  1909  for  additional 
quantities  of  his  serum.  Financial  constraints  had  prevented  him  from 
producing  additional  batches,  but  he  sent  what  he  had  on  hand,  even 
though  it  was  old  and  had  probably  lost,  in  his  estimate,  20  percent 
of  its  curative  value.  Since  the  efficacy  of  the  serum  had  not  been 
disproved,  Ricketts  was  reluctant  to  deny  it  to  those  who  sought  it. 
"From  the  humanitarian  standpoint,"  he  wrote  to  Tuttle,  "it  seems 
that  the  serum  should  be  supplied  until  it  has  been  shown  to  be  worth 
something  or  nothing."  Ricketts  also  noted  that  his  student  Paul  G. 
Heinemann  was  attempting  to  concentrate  the  serum  as  was  done  with 
diphtheria  antitoxin  to  make  it  more  effective. 

All  of  these  lines  of  research  were  suspended  or  slowed  down  in 
1909  because  of  one  insurmountable  obstacle:  money.  In  1907  the 
Montana  state  legislature  had  appropriated  two  thousand  dollars  for 
Ricketts's  work,  but  it  was  completely  used  up  during  that  year.  In 
1908  Missoula  and  Ravalli  counties  appropriated  five  hundred  dollars 
each,  and  the  state  board  of  health  contributed  five  hundred  dollars, 
a  total  of  fifteen  hundred  dollars  that  was  also  rapidly  consumed. 
Ricketts  and  Tuttle  also  appealed  to  Idaho  authorities  for  financial 
support,  noting  that  spotted  fever  afflicted  their  citizens  as  well.  It  was 
a  futile  request.  Idaho  apparently  felt  no  obligation  to  appropriate 
funds  for  what  was  perceived  as  Montana's  unique  problem. 

In  March  1909  the  Montana  state  legislature  committed  itself  to 
continuing  Ricketts's  work  through  a  special  bill  appropriating  six 
thousand  dollars  for  two  years'  investigations.  Ricketts  was  gratified, 
observing  to  Tuttle  that  it  was  "quite  a  remarkable  thing  for  a  state 
legislature  to  fall  in  with  the  plans  of  the  State  Board  of  Health  so 
harmoniously  in  the  interests  of  public  health. "^^  Unfortunately,  the 
state  legislature  had  voted  to  expend  more  monies  than  would  be 
collected  in  revenues.  Since  the  Montana  state  constitution  required  a 
balanced  budget,  the  task  of  reconciling  revenues  with  outlays  was 
given  to  the  State  Board  of  Examiners,  the  body  appointed  to  oversee 
the  state's  finances.  In  order  to  assure  funding  of  the  essential  state 
projects,  authorized  by  public  bills,  the  examiners  suspended  appro- 
priations for  all  special  bills  enacted  in  1909  until  revenue  was  increased 
to  cover  them.  Funds  for  the  spotted  fever  investigations  were  not  the 


Dr.  Rtcketts's  Discoveries 


69 


only  ones  withheld;  those  for  the  state  agricultural  experiment  station, 
for  example,  were  similarly  impounded/ ° 

The  examiners'  decision  came  just  before  the  1909  tick  season  in 
the  Bitterroot  Valley.  Miles  Romney,  proprietor  of  the  Western  News, 
informed  Tuttle  about  an  early  spotted  fever  death  that  spring  and 
pleaded  with  the  state  board  of  health,  "in  the  interest  of  common 
humanity,"  to  allow  Ricketts's  work  to  proceed.  No  large  local  sub- 
scription drive  or  appropriation,  however,  was  undertaken  to  replace 
the  impounded  state  money.  To  demonstrate  appreciation  for  Ricketts's 
work,  the  University  of  Montana,  at  the  urging  of  the  Montana  Medical 
Association,  conferred  on  him  an  honorary  degree  at  its  1909  com- 
mencement.'^ 

Although  no  one  was  able  to  budge  the  State  Board  of  Examiners 
from  its  fiscal  decision,  members  of  the  state  board  of  health  suggested 
to  Ricketts  that  if  he  could  obtain  funds  from  a  private  source,  such 
as  the  university  or  the  associated  John  Rockefeller  McCormick  Me- 
morial Institute  for  Infectious  Diseases,  the  funds  would  eventually  be 
released  and  the  state  would  pay  him  back."^  For  those  institutions, 
however,  the  probability  that  Montana  would  raise  the  needed  reve- 
nues was  too  uncertain  to  convince  them  that  this  would  be  a  wise 
course  of  action.  Ricketts's  spotted  fever  work  had  earned  him  a  gold 
medal  from  the  American  Medical  Association  as  well  as  several  offers 
of  professorships  from  universities,  and  it  was  difficult  for  the  rising 
research  star  to  stop  productive  investigations  until  money  again  be- 
came available. 

During  the  summer  of  1909,  Ludvig  Hektoen  urged  Ricketts  to 
consider  working  on  tabardillo,  the  Mexican  typhus  fever  named  for 
the  rash  that  resembled  a  red  cloak  on  its  victims.  This  disease,  Hektoen 
noted,  had  many  characteristics  in  common  with  spotted  fever,  and 
neither  its  cause  nor  its  means  of  transmission  was  known.  Later  noting 
that  he  would  have  decUned  or  postponed  his  work  on  typhus  had  he 
"known  surely  that  .  .  .  [Montana  authorities]  would  come  up  with 
the  money,"  Ricketts  decided  that  he  must  go  forward  in  some  line 
of  research.  Hektoen  arranged  for  the  Mexican  government,  the  Uni- 
versity of  Chicago,  and  the  Memorial  Institute  to  share  the  financing 
of  the  project.  Since  the  annual  epidemics  of  tabardillo  usually  started 
in  late  autumn,  Ricketts  left  for  Mexico  City  in  December  1909.^'* 

Only  after  arriving  in  Mexico  did  Ricketts  learn  that  a  French  re- 
searcher, Charles  Nicolle,  working  in  Tunis,  Africa,  had  recently  dem- 
onstrated the  body  louse  as  the  vector  of  typhus.  In  addition.  Hygienic 
Laboratory  researchers  John  F.  Anderson,  who  had  investigated  spot- 


70 


Rocky  Mountain  Spotted  Fever 


ted  fever  in  1903,  and  Joseph  Goldberger,  who  suffered  a  bout  with 
typhus  while  studying  it,  had  confirmed  Nicolle's  findings  and  suc- 
ceeded in  directly  inoculating  the  typhus  pathogen  into  monkeys. 
Gamely  proceeding  with  his  work  even  though  he  had  lost  the  chance 
to  claim  priority,  Ricketts  and  his  student  Russell  M.  Wilder  also 
confirmed  these  findings.  More  importantly,  they  described  an  orga- 
nism similar  to  the  spotted  fever  organism  that  was  consistently  found 
in  the  blood  of  patients,  in  the  lice  that  fed  on  these  patients,  and  in 
the  feces  of  the  infected  lice.^^ 

Shortly  after  the  new  year,  Thomas  D.  Tuttle,  secretary  of  the  Mon- 
tana State  Board  of  Health,  received  word  that  the  State  Board  of 
Examiners  had  released  the  funds  for  spotted  fever  work.  A  relieved 
Ricketts,  who  had  recently  accepted  a  professorship  at  the  University 
of  Pennsylvania  and  was  preparing  to  leave  Chicago,  wrote  Tuttle  that 
he  hoped  the  19 10  work  — a  "pretty  heavy  piece  of  work"  on  "the 
role  of  the  small  wild  animals"— would  conclude  his  spotted  fever 
investigations.  Ricketts  projected  that  he  would  be  able  to  leave  Mexico 
City  by  20  April  and  would  be  in  Montana  in  mid  May.  Tuttle,  however, 
urged  him  to  come  even  sooner,  assuring  him  that  the  state  would 
fund  all  necessary  expenses,  including  the  salaries  of  his  assistants. 
"Employ  such  men  as  you  need,"  Tuttle  wrote,  but  "for  goodness' 
sake  get  them  out  as  soon  as  possible,  as  the  weather  is  getting  very 
warm  and  the  ticks  are  coming  out."^^ 

From  his  lodgings  at  the  American  Club  in  Mexico  City,  Ricketts 
wrote  to  his  student  Josiah  J.  Moore,  instructing  him  to  proceed  to 
Montana,  but  Ricketts  himself  continued  to  work  on  tabardillo.  The 
work  was  dangerous,  for  the  tiny  lice  that  had  been  implicated  as  the 
vectors  of  the  disease  were  often  difficult  to  detect.  Ricketts  avoided 
the  hospital  in  which  typhus  patients  were  treated.  The  medical  staff, 
he  observed,  were  "very  filthy  in  the  care  of  their  patients,"  and  living 
Hce  could  be  found  in  the  bed  linens  of  victims  "almost  any  day." 
Except  for  comments  to  trusted  scientific  colleagues,  Ricketts  said  little 
of  the  peril  in  which  he  worked.  "Mrs.  Ricketts  is  more  or  less  worried 
now,"  he  confided  to  one  friend,  "and  if  she  should  learn  about  .  .  . 
[the  hospital  conditions],  I  think  I  should  have  to  go  home  in  order 
to  quiet  her  fears. "^^ 

In  mid  April,  Ricketts  did  become  infected  with  typhus.  Russell  M. 
Wilder  communicated  this  unfortunate  turn  of  events  to  Tuttle  but 
added  optimistically,  "I  have  every  reason  to  believe  that  Dr.  Ricketts 
will  make  a  safe  recovery  from  his  illness."  Ricketts  was  only  thirty- 
nine  and,  like  Goldberger  before  him,  should  probably  have  been  able 
to  fight  off  the  disease.  Throughout  the  fall  of  1909,  however,  Ricketts 


Dr.  Ricketts's  Discoveries 


71 


referred  to  an  unnamed  illness  that  periodically  plagued  him  and  pos- 
sibly lowered  his  resistance.  On  3  May  19 10  he  succumbed  to  typhus 
in  Mexico.  In  Montana  the  news  was  grimly  received.  "In  the  midst 
of  his  experiments,"  said  the  Daily  Missoulian,  "the  man,  beloved  in 
Montana  and  honored  in  the  world  of  learning,  was  stricken  by  the 
very  ailment  for  which  he  sought  a  remedy.""^ 

Ricketts's  death  brought  spotted  fever  investigations  to  an  abrupt 
halt.  Tuttle  wired  Josiah  J.  Moore,  who  had  already  arrived  in  the 
Bitterroot  and  established  a  camp,  to  make  up  a  statement  of  expenses 
and  return  to  Chicago.  Since  the  Montana  state  legislature  had  ap- 
propriated funds  specifically  for  Ricketts's  use,  not  even  Moore  — a 
Montana  native  of  "exceptionable  abihty"  who  had  worked  with 
Ricketts  for  three  years  on  spotted  fever— was  authorized  to  carry  on 
the  investigations.^^  A  few  experiments  already  underway  were  pub- 
hshed,  many  in  a  memorial  volume  prepared  by  Ricketts's  colleagues 
and  students. Tuttle  corresponded  in  vain  with  several  of  Ricketts's 
associates,  hoping  that  they  might  continue  the  work.^^  Without  the 
leadership  of  the  dynamic  Ricketts,  however,  laboratory  experimen- 
tation on  spotted  fever  virtually  ceased. 

In  the  short  space  of  three  years,  Howard  Taylor  Ricketts  had  re- 
directed scientific  thinking  about  Rocky  Mountain  spotted  fever.  Mov- 
ing beyond  the  dogma  surrounding  arthropod  transmission  of  disease, 
he  demonstrated  that  spotted  fever  was  indeed  tick  borne  and  that 
infected  ticks  existed  in  nature.  His  studies  of  the  tick  produced  a  plan 
for  controlling  the  pests  and  their  mammalian  hosts.  With  relentless 
persistence,  he  pursued  techniques  for  producing  a  vaccine  and  anti- 
serum against  the  disease.  Trusting  his  experimental  observations, 
Ricketts  refused  to  be  discouraged  by  his  inability  to  culture  the  spotted 
fever  organism  in  accordance  with  Koch's  postulates.  Although  his 
untimely  death  cut  short  further  work,  each  line  of  research  was  pro- 
ductively followed  by  his  successors  in  spotted  fever  work.  Ricketts's 
contributions  were  recognized  by  his  scientific  peers  when  the  group 
of  diseases  to  which  spotted  fever  and  typhus  belong  was  named 
rickettsial  in  his  honor.  For  the  people  of  the  Bitterroot  Valley,  his 
expertise  and  imagination  provided  not  only  a  hope,  unfulfilled,  for 
an  effective  antiserum,  but  also  a  focus,  the  tick,  for  efforts  against 
the  dread  disease. 


Chapter  Five 


Tick  Eradication  Efforts, 

IpII-I^lO 

When  the  devil  made  the  tick,  he  overlooked  a  bet  in  not  giving  it  wings. 

Bitterroot  Valley  rancher,  19 19 


If  the  first  decade  of  spotted  fever  research  in  the  Bitterroot  Valley 
belonged  to  bacteriologists,  the  second  decade  clearly  was  dominated 
by  entomological  control  methods.  Since  no  effective  medical  preven- 
tive or  therapy  had  been  developed  for  spotted  fever,  an  attack  on  the 
tick  itself  seemed  the  only  immediate  hope  of  ridding  the  valley  of  its 
scourge.  Texas  cattle  fever  was  being  controlled  in  the  southern  states 
with  a  rigorous  vector  control  program,  Major  William  Crawford 
Gorgas  of  the  U.S.  Army  had  dramatically  demonstrated  in  Havana 
that  yellow  fever  could  be  halted  with  mosquito  control  methods,  and 
the  U.S.  Public  Health  and  Marine  Hospital  Service  had  suppressed 
bubonic  plague  epidemics  in  San  Francisco  and  New  Orleans  by  at- 
tacking fleas  and  their  host  rats.  These  successful  campaigns  inspired 
hope  that  spotted  fever  could  be  eliminated  in  a  similar  manner. 

It  was  not  until  the  late  nineteenth  century  that  ticks  were  identified 
as  carriers  of  pathogenic  microorganisms,  but  they  had  been  recognized 
as  unwelcome  parasites  at  least  as  early  as  550  B.C.,  when  Homer 
described  the  sufferings  of  an  infested  dog.  The  misery-causing  po- 
tential of  ticks  was  somewhat  offset  by  allegedly  therapeutic  quaHties 
for  which  they  were  valued.  In  ancient  Chinese  medicine  white  cattle 
ticks  were  ground  with  rice  powder,  formed  into  cakes,  and  admin- 
istered to  children  as  a  preventive  for  smallpox.  Galen  and  other 
authorities  of  late  antiquity,  whose  medical  opinions  continued  to 
dominate  the  thought  of  the  Middle  Ages,  recommended  the  crushed 
bodies  of  ticks  for  a  variety  of  medical  problems.  Used  as  a  paste  or 
taken  in  wine,  ticks  were  employed  as  aphrodisiacs  and  used  to  clean 
ulcerations,  to  arrest  menstruation,  to  prevent  the  regrowth  of  un- 
wanted hair,  and  to  treat  anal  fistula.^ 


72 


Ticks  waiting  on  vegetation 
for  a  host  to  pass  by. 
(Courtesy  of  the  Rocky 
Mountain  Laboratories, 
MAID.) 


From  the  Renaissance  until  the  nineteenth  century,  ticks  were  rarely 
mentioned  in  medical  treatises.  By  the  time  Theobald  Smith  and  Fred 
L.  Kilbourne  discovered  that  the  cattle  tick  transmitted  a  pathogenic 
protozoan  organism,  however,  zoology  had  become  a  flourishing  en- 
terprise in  universities,  hence  much  was  already  known  about  ticks 
themselves.  In  zoological  classification  schemes  ticks  resided  in  the 
phylum  Arthropoda,  comprised  of  creatures  having  segmented  bodies 
with  paired  jointed  appendages  and  an  exoskeleton.  Containing  more 
species  than  all  other  phyla  combined,  the  arthropods  encompassed 
insects,  centipedes,  crabs,  lobsters,  mites,  and  scorpions  as  well  as 
ticks.  Ticks,  mites,  and  scorpions— arthropods  having  eight  legs,  no 
wings  or  antennae,  simple  eyes,  if  any,  and  a  fused  head  and  thorax— 
were  further  subdivided  into  the  class  Arachnida.  Within  this  class, 
the  order  Acarina  included  ticks  and  mites  but  excluded  scorpions. 
Ticks  alone  were  placed  into  the  superfamily  Ixodoidea,  which  con- 
tained two  families,  the  Argasidae  and  the  Ixodidae.  These  were  com- 
monly known  as  soft  ticks  and  hard  ticks,  respectively,  because  the 
latter  possessed  a  shield  or  scutum  that  partially  covered  their  backs. 


74 


Rocky  Mountain  Spotted  Fever 


Among  the  hard  ticks,  the  Dermacentor  genus  was  widespread  in  the 
United  States  and  contained  many  species.^ 

When  first  suspected  of  transmitting  Rocky  Mountain  spotted  fever, 
ticks  were  generally  described  in  nonspecific  terms.  In  their  initial  1902 
report,  Louis  B.  Wilson  and  William  M.  Chowning  spoke  of  spotted 
fever  as  a  disease  carried  by  "a  tick."^  They  sent  specimens  to  zoologist 
Charles  Wardell  Stiles  at  the  Hygienic  Laboratory  of  the  U.S.  PubHc 
Health  and  Marine  Hospital  Service  in  Washington,  D.C.,  for  his  expert 
determination,  as  did  John  F.  Anderson  the  following  year.  Possibly 
influenced  by  Wilson  and  Chowning's  claim  that  a  Piroplasma  was 
the  cause  of  spotted  fever.  Stiles  provisionally  determined  that  the  tick 
was  Dermacentor  reticulatus,  the  same  tick  that  transmitted  a  piro- 
plasmic  disease  to  dogs.  The  zoologist  stipulated,  however,  that  further 
study  was  necessary  for  a  definite  determination  because  of  certain 
differences  he  had  observed  between  the  Rocky  Mountain  wood  tick 
and  D.  reticulatus.'^  When  Stiles  published  the  report  of  his  own  in- 
vestigation into  spotted  fever,  he  called  the  tick  Dermacentor  ander- 
soni.  This  new  name,  by  which  he  honored  his  colleague  John  F. 
Anderson,  implied  that  the  tick  was  a  separate  species.  Stiles  mentioned 
the  name  only  once,  however,  and  he  provided  no  description  of 
uniqueness.  Both  Walter  W.  King  and  Howard  Taylor  Ricketts  called 
the  tick  used  in  their  transmission  experiments  Dermacentor  occiden- 
talism which  was  actually  a  common  California  tick.  Ricketts  continued 
to  use  this  name  until  1909.^ 

In  June  1908,  Nathan  Banks,  a  specialist  on  ticks  with  the  U.S. 
Bureau  of  Entomology,  seemed  to  resolve  the  confusing  nomenclature 
when  he  published  "A  Revision  of  the  Ixodoidea,  or  Ticks,  of  the 
United  States,"  describing  and  defining  the  Rocky  Mountain  wood 
tick  as  Dermacentor  venustus  (Banks). ^  Less  than  a  month  later,  how- 
ever. Stiles  refuted  Banks's  claim,  maintaining  that  D.  venustus  was  a 
Texas  tick  with  different  characteristics  and  that  his  1905  designation, 
D.  andersoni  (Stiles),  should  be  retained.  In  August  1910,  Stiles  pub- 
lished a  detailed  scientific  study  on  the  value  of  microscopic  structural 
differences  in  choosing  names  for  Dermacentor  ticks.  This  new  re- 
search. Stiles  argued,  proved  his  designation  D.  andersoni  beyond 
doubt.  Banks,  in  contrast,  continued  to  support  his  claim  that  D. 
venustus  was  the  identical  tick  and  that  his  1908  published  description 
estabhshed  priority.^ 

After  19 10  the  inconclusive  war  of  names  stalemated.  Entomologists 
continued  to  call  the  tick  D.  venustus^  and  physicians  from  Stiles's 
agency,  the  U.S.  Public  Health  and  Marine  Hospital  Service,  always 
referred  to  D.  andersoni.  Reports  from  the  two  groups  appeared  side 


Tick  Eradication  Efforts,  ipii-ipio 


75 


by  side  in  official  Montana  publications,  utilizing  the  two  different 
names  without  explanation  or  apology  to  the  lay  reader,  who  must 
have  been  somewhat  confused  if  not  familiar  with  the  controversy.^ 
In  1923  the  question  was  submitted  to  the  International  Commission 
on  Zoological  Nomenclature,  an  official  body  created  to  resolve  such 
disputes.  Although  a  member,  Stiles  did  not  vote  because  of  his  personal 
involvement  in  the  case.  DecHning  to  judge  which  tick  carried  the 
disease,  the  commission  took  a  narrow  approach  to  the  types  of  speci- 
mens represented  by  Stiles's  and  Banks's  names.  The  majority  opinion 
declared  that  Dermacentor  venustus  belonged  to  a  form  with  a  Texas 
tick  as  a  holotype  and  that  Dermacentor  andersoni  belonged  to  a  form 
with  a  tick  from  Woodman,  Montana,  as  the  holotype.  Since  spotted 
fever  was  unknown  in  Texas  at  that  time,  D.  andersoni  became  the 
official  name  for  the  spotted  fever  tick.^ 

This  taxonomic  tempest  embodied  on  a  superficial  level  a  deeper 
internecine  rivalry  between  physicians  and  entomologists.  Before  the 
link  between  arthropods  and  disease  had  been  established,  each  group's 
areas  of  expertise  seemed  clearly  defined:  physicians  treated  sick  peo- 
ple; entomologists  primarily  assisted  farmers  in  eliminating  crop-de- 
stroying insects.  A  relatively  new  professional  group,  entomologists 
were  still  struggling  to  establish  a  separate  identity  from  zoology,  their 
older  and  broader  parent  disciphne.^° 

During  the  earliest  period  of  white  settlement  of  North  America, 
there  had  been  no  need  for  such  specially  trained  scientists  because 
indigenous  insects  rarely  caused  problems  for  farmers.  After  the  Amer- 
ican Revolution,  however,  the  gradual  normalization  of  trade  led  to 
the  importation  of  foreign  plants,  some  of  which  harbored  injurious 
insects  that  multiplied  rapidly.  Individual  states  began  to  employ  en- 
tomologists during  the  1840s,  and  in  1854  the  U.S.  Patent  Office 
employed  a  person  to  collect  statistics  on  seeds,  fruits,  and  insects. 
Specialists  in  entomology  were  few  and  the  literature  sparse  throughout 
the  1 8 60s,  even  though  the  1862  act  establishing  the  Department  of 
Agriculture  boosted  the  status  of  entomologists  by  authorizing  their 
employment  to  provide  useful  information  for  farmers.  The  1874-76 
flight  of  locusts  from  Montana  and  the  Dakotas  as  far  south  as  Missouri 
focused  additional  attention  on  the  devastation  that  insects  could  cause 
and  led  to  the  formation  of  a  federal  entomological  commission  to 
study  the  depredations  of  the  locusts.  In  1887,  partly  as  a  result  of 
the  commission's  reports.  Congress  authorized  the  establishment  of 
agricultural  experiment  stations  that  included  speciaHsts  in  entomol- 
ogy.'' 

The  development  of  graduate  programs  in  universities  and  the  es- 


76 


Rocky  Mountain  Spotted  Fever 


tablishment  of  professional  societies,  such  as  the  Association  of  Eco- 
nomic Entomologists,  founded  in  1889,  also  advanced  entomology  as 
a  profession.  Post-Civil  War  industrialization  and  urbanization  en- 
hanced this  trend,  altering  traditional  cultural  patterns  and  fostering 
the  development  of  expert  knov^^ledge  in  a  variety  of  fields.  The  term 
medical  entomology  was  coined  in  1909  for  the  specific  study  of  ar- 
thropods and  disease,  but  actual  professional  differentiation  remained 
far  from  rigid.  Zoologists  interested  in  all  forms  of  parasitism  studied 
arthropods  as  well  as  worms,  bacteria,  and  protozoa.  With  the  dis- 
coveries in  the  1890s  that  arthropods  could  transmit  pathogenic  mi- 
croorganisms to  animals  and  humans,  veterinarians,  physicians,  and 
public  health  researchers  also  became  interested  in  the  field.  As  these 
groups  pursued  overlapping  goals,  professional  rivalries  often  marred 
the  more  altruistic  aim  of  selfless  devotion  to  the  advancement  of 
science. 

Physicians,  who  had  a  much  longer  professional  history  than  most 
other  groups  and  whose  status  was  rising  with  each  new  bacteriological 
triumph,  were  often  accused  of  ignoring  or  subordinating  the  contri- 
butions of  other  professions.^^  For  human  diseases,  physicians  coun- 
tered such  criticism  with  the  observation  that  they  alone  were  properly 
trained  to  apply  speciaHzed  knowledge  to  a  pubHc  health  problem. 
Because  Rocky  Mountain  spotted  fever  was  transmitted  by  ticks,  both 
physicians  and  entomologists  were  interested  in  its  control.  Unfortu- 
nately, a  bitter  power  struggle  developed  between  the  two  groups  in 
Montana  that  reverberated  to  the  federal  level  and  retarded  coordi- 
nation of  the  effort. 

Initially  this  struggle  centered  on  two  strong-willed  men,  Thomas 
D.  Tuttle,  secretary  of  the  Montana  State  Board  of  Health,  and  Robert 
A.  Cooley,  the  Montana  state  entomologist.  Tuttle,  who  had  fought 
for  increased  funding  for  pubhc  health  and  had  vigorously  enforced 
local  health  ordinances,  assumed  after  the  death  of  Howard  Taylor 
Ricketts  that  the  Montana  State  Board  of  Health  would  continue  to 
direct  the  attack  on  Rocky  Mountain  spotted  fever.  In  March  19 11 
he  appealed  to  Surgeon  General  Walter  Wyman  of  the  U.S.  Pubhc 
Health  and  Marine  Hospital  Service  to  send  a  new  researcher  who 
could  utilize  state  funds  appropriated  for  spotted  fever  research.  Wy- 
man stalled,  citing  the  heavy  demands  on  Service  officers.  After  con- 
tinued appeals  from  Tuttle  and  Montana  Senators  Paris  Gibson  and 
Henry  L.  Myers,  however,  Wyman  relented  and  in  mid  May  detailed 
Passed  Assistant  Surgeon  Thomas  B.  McClintic  to  Montana. 

A  thirty-eight-year-old  graduate  of  the  University  of  Virginia  Med- 
ical School  and  twelve-year  veteran  Service  officer,  McClintic  had 


Tick  Eradication  Efforts,  i^ii-ipzo 


77 


considerable  experience  in  quarantine  work,  both  in  the  United  States 
and  abroad,  including  "the  usual  tour  of  duty  of  officers  in  the  tropics." 
During  several  periods  when  he  was  stationed  at  the  Hygienic  Lab- 
oratory, McChntic  had  been  found  to  have  a  "special  fitness  for  re- 
search work,"  and  it  was  the  combination  of  field  experience  and 
laboratory  expertise  that  induced  Wyman  to  select  him  as  the  officer 
who  would  tackle  the  mysterious  spotted  fever.  During  the  summer 
of  191 1,  McClintic  hoped  to  demonstrate  the  practicabiHty  of  pre- 
venting spotted  fever  in  the  limited  area  around  Victor,  Montana, 
using  tick  control  principles  outlined  by  Ricketts.^^ 

On  his  way  to  the  Bitterroot,  McClintic  stopped  in  Bozeman,  Mon- 
tana, to  consult  with  Cooley,  the  state  entomologist,  who  had  been 
researching  the  life  cycle  and  habits  of  the  tick.  To  his  surprise, 
McClintic  found  that  Cooley  had  already  raised  a  subscription  to 
construct  an  experimental  dipping  vat  for  tick  control  in  the  Florence 
area,  about  fifteen  miles  north  of  Victor.  This  project,  Cooley  noted, 
was  actually  funded  and  staffed  by  representatives  of  the  U.S.  Bureau 
of  Entomology  and  the  U.S.  Bureau  of  Biological  Survey.  When 
McClintic  and  Tuttle  arrived  in  Florence  three  days  later  to  assess  the 
situation,  they  were  utterly  astonished  to  discover  Cooley  in  the  field, 
supervising  the  project  himself. 

Having  known  nothing  about  the  experimental  dipping  vat  and, 
perhaps  more  importantly,  having  expended  great  effort  to  persuade 
the  U.S.  Public  Health  and  Marine  Hospital  Service  to  resume  spotted 
fever  work,  Tuttle  experienced  embarrassment  that  rapidly  turned  to 
fury.  It  appeared  clear  to  him  that  the  entomologists  were  meddling 
in  a  public  health  matter. Tuttle  and  other  members  of  the  Montana 
State  Board  of  Health  immediately  undertook  efforts  to  force  the 
perceived  interlopers  out  of  spotted  fever  work,  but  Cooley  proved  as 
adamant  as  Tuttle,  and  the  hostility  between  the  two  men  intensified. 

Robert  A.  Cooley,  the  focus  of  Tuttle's  concern,  was  born  on  27 
June  1873  Deerfield,  Massachusetts.  After  receiving  a  B.S.  degree 
in  1895  ^^om  Massachusetts  Agricultural  College,  Cooley  completed 
four  additional  years  of  graduate  work  in  the  pioneer  entomological 
graduate  school  of  that  institution.^^  Before  fulfilling  all  the  require- 
ments for  his  Ph.D.,  however,  he  accepted  a  position  as  professor  of 
zoology  and  entomology  at  the  Montana  State  College  in  Bozeman. 
Since  the  college  housed  the  state  agricultural  experiment  station,  Coo- 
ley also  assumed  duties  as  the  station  entomologist.  In  1903  he  helped 
write  legislation  that  conferred  upon  the  agricultural  station  ento- 
mologist the  additional  title  of  Montana  state  entomologist.  A  man 
who  inspired  intense  loyalty  in  his  friends  and  students,  Cooley,  Hke 


78 


Rocky  Mountain  Spotted  Fever 


Robert  A.  Cooley,  secretary 
of  the  Montana  State  Board 
of  Entomology,  championed 
Hvestock  dipping  to  eUminate 
the  spotted  fever  tick  from  the 
Bitterroot  Valley.  He  hoped  to 
repeat  the  success  of  southern 
entomologists  who  had  con- 
trolled Texas  cattle  fever,  an- 
other tick-borne  disease,  by 
this  method.  (Courtesy  of  the 
Rocky  Mountain  Laborato- 
ries, NIAID.) 

Tuttle,  had  a  stubborn  streak  that  made  him  unwilling  to  compromise 
when  facing  someone  he  perceived  as  an  adversary. 

Cooley  first  entered  spotted  fever  work  as  a  result  of  Ricketts's 
recommendation  that  the  Montana  State  Board  of  Health  locate  an 
entomologist  to  launch  long-range,  year-round  studies  of  the  spotted 
fever  tick.  Having  no  idea  that  conflict  lay  ahead,  Tuttle  logically  sought 
assistance  from  the  state  entomologist.  In  1908,  Cooley  and  his  student 
Willard  V.  King  began  to  study  Montana  ticks  in  a  noninfected  area 
near  Bozeman  and  formulated  plans  to  repeat  Ricketts's  work  on  the 
tick's  life  cycle.  Ricketts,  who  was  not  entirely  pleased  that  Cooley 
chose  to  repeat  these  experiments,  commented  to  Tuttle  that  Cooley 
seemed  little  inclined  "to  concede  that  the  direction  of  his  work  should 
be  guided  by  my  results  and  conclusions."  Cooley's  efforts  to  raise  a 
separate  fund  from  Missoula  and  RavaUi  counties  for  entomological 
work  on  spotted  fever,  Ricketts  continued,  also  suggested  that  Cooley 
"was  inclined  to  carry  on  his  work  independently."  Tuttle  had  found 
Cooley  unwilling  to  allow  the  report  on  his  1908  work  to  be  incor- 
porated in  the  state  board  of  health's  biennial  report.  Cooley  preferred 
to  publish  it  with  his  own  report  as  state  entomologist  since  the  work 
had  been  done  with  funds  from  that  office. 

During  the  winter  of  1908-9,  Cooley  traveled  to  Washington,  D.C., 
and  consulted  with  representatives  of  the  U.S.  Bureau  of  Entomology, 


Tick  Eradication  Efforts,  i^ii-i^zo 


79 


who  had  already  sponsored  a  tick  survey  of  the  northwest  states  in 
which  Willard  V.  King  had  participated.  Since  the  range  of  the  Rocky 
Mountain  wood  tick  was  found  to  extend  from  the  northern  edge  of 
New  Mexico  to  Canada  and  from  CaHfornia's  Cascade  range  to  the 
western  Great  Plains,  plans  were  laid  for  a  collaborative  study  between 
the  U.S.  Bureau  of  Entomology  and  the  U.S.  Bureau  of  Biological 
Survey,  the  federal  agency  charged  with  wildlife  surveys  and  control 
of  animal  pests,  to  investigate  further  the  hosts  and  habits  of  the  disease- 
bearing  tick.^°  During  the  spring  of  19 lo,  while  the  Montana  State 
Board  of  Health  awaited  Ricketts's  arrival  only  to  be  devastated  by 
news  of  his  death,  Cooley  established  a  field  station  in  the  Bitterroot 
Valley  on  Sweeney  Creek,  southwest  of  Florence,  an  area  known  to 
be  infected  with  spotted  fever.  Calling  the  station  Camp  Venustus  after 
Nathan  Banks's  designation  of  the  spotted  fever  tick,  Cooley  assembled 
three  representatives  from  federal  agencies  to  conduct  the  study:  Wil- 
lard V.  King  from  the  U.S.  Bureau  of  Entomology  and  Arthur  H.  Howell 
and  Clarence  Birdseye  from  the  U.S.  Bureau  of  Biological  Survey. 
Birdseye,  who  later  developed  a  technique  for  freezing  foods  and 
launched  the  company  that  bears  his  name,  was  embarking  on  his  first 
practical  research  as  a  young  college  graduate.  Howell,  the  group's 
senior  member,  returned  east  after  a  short  time.  Purportedly,  King  and 
Birdseye,  seeking  first-author  privileges  on  the  publications  that  were 
expected  to  result,  employed  an  elaborate  practical  joke  to  scare  Howell 
into  believing  that  he  had  been  bitten  by  a  potentially  infected  tick.^^ 
In  order  to  protect  themselves,  King  and  Birdseye  developed  a  num- 
ber of  methods  that  became  standard  procedure  for  field  studies  of 
spotted  fever.  They  wore  high-topped  shoes  to  which  were  attached 
pieces  of  khaki  cloth  fastened  by  drawstrings  higher  up  on  the  leg.  To 
their  cotton  outer  garments,  they  applied  kerosene  as  a  tick  repellent, 
a  measure  that  seemed  to  be  useful,  at  least  until  the  kerosene  evap- 
orated. At  night  they  fumigated  their  clothing  in  an  airtight  closet  with 
bisulphide  of  carbon.  On  the  basis  of  Josiah  J.  Moore's  research  that 
an  infected  tick  had  to  feed  for  nearly  two  hours  in  order  to  transmit 
spotted  fever,  the  men  regularly  conducted  rigorous  examinations  of 
their  bodies  within  that  time  period.  This  regimen  proved  successful: 
although  occasional  bites  occurred,  neither  of  them  contracted  spotted 
fever. 

King  and  Birdseye  sought  to  determine  more  precisely  the  life  cycle 
of  the  tick  and  to  identify  its  hosts  in  each  stage.  Using  a  white  woolen 
or  flannel  cloth  attached  to  a  pole  hke  a  flag,  King  collected  ticks  from 
brush.  Birdseye  shot  and  trapped  717  small  wild  animals— thereby 
incurring  the  wrath  of  the  game  warden— and  collected  4,495  addi- 


8o 


Rocky  Mountain  Spotted  Fever 


Flagging  for  ticks  in  the  Bitterroot  Valley.  The  flannel  flags,  dragged  across 
brush  vegetation  favored  by  ticks,  were  used  to  obtain  ticks  for  entomolog- 
ical studies  and  for  spotted  fever  vaccine  production.  The  collector  pro- 
tected himself  by  tucking  his  pants  into  his  boots,  by  w^earing  long-sleeved 
clothing,  and  by  inspecting  his  body  at  regular  intervals.  (Courtesy  of  the 
Rocky  Mountain  Laboratories,  NIAID.) 


tional  ticks/^  Samples  of  different  species  were  sent  to  the  Dallas, 
Texas,  station  of  the  U.S.  Bureau  of  Entomology  to  be  reared  and 
identified.  King's  studies  established  that  the  spotted  fever  tick  did  not 
complete  its  Hfe  cycle  in  one  year,  as  Ricketts  believed,  but  instead 
had  at  least  a  two-year  life  cycle,  spending  the  winter  either  as  an  adult 
or  as  a  nymph.  Birdseye  determined  that  the  immature  stages  of  the 
tick  fed  on  a  variety  of  small  animals  while  the  adult  ticks  fed  exclu- 
sively on  large  animals  such  as  horses,  cows,  sheep,  and  goats.  When 
he  assessed  these  findings,  Cooley  concluded  that  the  spotted  fever  tick 
might  be  eliminated  Hke  the  Texas  cattle  fever  tick— by  preventing 
adults  from  reaching  a  host  on  which  to  feed  and  breed.  Birdseye's 
observation  that  adult  ticks  fed  only  on  large  animals,  moreover,  sug- 
gested that  destroying  the  small  rodents  that  served  as  hosts  to  the 


Tick  Eradication  Efforts,  ipii-ipio 


8i 


larval  and  nymphal  tick  stages  might  be  completely  unnecessary.^"^ 

As  this  work  was  being  completed,  Tuttle  was  preparing  the  biennial 
report  of  the  state  board  of  health.  Perhaps  wishing  to  include  some 
positive  note  on  progress  in  spotted  fever  research  to  lessen  the  impact 
of  Ricketts's  death,  Tuttle  again  invited  Cooley  to  incorporate  a  full 
or  summary  report  of  the  entomological  work,  or,  at  a  minimum,  a 
mention  that  cooperative  work  was  taking  place.  On  the  advice  of 
W.  D.  Hunter  of  the  U.S.  Bureau  of  Entomology,  however,  Cooley 
again  chose  to  pubhsh  his  findings  separately.^^' 

During  the  fall  and  winter  of  19  lo,  Cooley  sought  funds  to  imple- 
ment a  tick  control  program  from  Governor  Edwin  L.  Norris  and  from 
W.  E.  McMurry,  Ravalli  County's  representative  to  the  Montana  state 
legislature.  Cooley  asserted  that  the  execution  of  his  plan  was  "purely 
an  Entomological  matter"  and  asked  for  ten  thousand  dollars  over 
two  years  either  for  the  use  of  the  state  entomologist  or  for  the  state 
board  of  health  with  the  specification  that  the  money  was  for  tick 
eradication  under  the  direction  of  the  state  entomologist.  Although 
neither  state  official  seemed  inclined  to  support  this  request,  Cooley 
intimated  to  several  people  that  Tuttle  might  be  persuaded  to  turn  over 
all  or  a  portion  of  the  two-thousand-dollar  state  board  of  health  ap- 
propriation to  him  for  tick  eradication  work.  After  the  incident  with 
McClintic,  however,  Tuttle  would  scarcely  have  allocated  Cooley  a 
dime.^^ 

With  no  state  money  available,  Cooley's  19 11  program  went  for- 
ward under  continued  funding  from  the  U.S.  Bureaus  of  Entomology 
and  Biological  Survey.  Stationed  at  an  abandoned  saloon  in  Florence, 
King  conducted  experiments  to  determine  how  long  ticks  could  survive 
without  feeding,  and  Birdseye,  who  maintained  that  rodent  destruction 
was  indeed  necessary,  developed  an  improved  formula  of  poisoned 
rolled  oats.^^  In  King's  longevity  experiments,  conducted  outside  Flor- 
ence at  the  same  cabin  on  Sweeney  Creek  used  the  year  before,  ticks 
were  placed  in  tubes  in  the  ground.  A  plug  of  earth  in  the  bottom 
prevented  their  escape  but  ensured  contact  with  ground  moisture. 
Although  a  "man  and  animal  proof  fence"  was  built  and  a  caretaker 
hired,  the  experiment  was  judged  by  Tuttle  to  constitute  a  menace  to 
the  surrounding  citizenry,  and  Cooley,  on  the  advice  of  his  superior 
at  the  college,  reluctantly  removed  them.^^ 

In  May  19 11,  just  before  McClintic  arrived  in  the  Bitterroot,  Cooley 
published  an  outhne  for  control  of  spotted  fever  based  primarily  on 
the  19 10  investigations.  His  principal  recommendation  appeared  in 
boldface  type:  "The  key  to  the  situation  seems  to  be  the  destruction 
of  ticks  on  domestic  animals  only."  Montana  newspapers  did  not  miss 


82 


Rocky  Mountain  Spotted  Fever 


the  implication  of  this  statement,  and  the  headUne  of  one  paper  pro- 
claimed, "Cooley  Sounds  the  Key  Note  to  Spotted  Fever  Eradication."^^ 

For  Tuttle  the  cumulative  effects  of  Cooley's  actions  inspired  outrage. 
The  new^spaper  headlines  indicated  that  Cooley  w^as  arrogating  to 
himself  the  program  outlined  in  1908  by  Ricketts,  whom  Tuttle  ad- 
mired greatly.  Cooley's  longevity  experiments  imphed  disregard  for 
pubHc  safety.  When  these  offenses  v^ere  added  to  Cooley's  persistent 
attempts  to  establish  and  fund  a  separate  entomological  program  for 
spotted  fever  eradication— not  to  mention  the  embarrassment  over  the 
incident  when  McClintic  arrived— Tuttle  and  his  colleagues  on  the 
state  board  of  health  determined  that  strong  action  was  necessary.  At 
its  meeting  on  5  June,  the  state  board  passed  a  resolution  asking 
Cooley's  employer,  the  state  board  of  education,  to  instruct  the  en- 
tomologist that  he  should  cooperate  with  the  work  of  the  state  board 
of  health  already  in  progress. ^° 

Apparently  nothing  came  of  this  request  and  the  situation  escalated, 
for  Tuttle  called  a  special  meeting  of  the  board  of  health  24  July.  He 
read  a  prepared  statement  outlining  in  detail  Cooley's  high  crimes  and 
misdemeanors.  In  addition  to  the  other  charges,  Tuttle  noted  that  in 
19 10,  Cooley  had  conducted  experiments  in  his  laboratory  at  Montana 
State  College  with  spotted  fever-infected  ticks.  The  four  guinea  pigs 
used  in  the  investigation  had  died,  but  Cooley  had  not  suspected  spotted 
fever  because  their  temperatures  had  not  risen  precipitously.  Only  when 
he  examined  the  body  of  the  last  dead  guinea  pig  did  Cooley  notice 
a  rash  and  the  characteristic  hemorrhagic  scrotum.  Tuttle  cited  this 
incident  as  a  dangerous  venture  into  work  that  should  have  been  done 
only  by  a  physician.  "Playing  with  dynamite  on  a  platform  where  there 
are  fireworks  being  discharged  is  a  mild  experiment  compared  with 
that  of  working  with  infected  ticks  in  a  school  or  college  by  one  who 
is  not  able  to  detect  such  a  fatal  disease  as  spotted  fever."  The  board, 
already  incensed,  resolved  to  raise  the  matter  more  strongly  with  the 
state  board  of  education.  "We  must  uphold  Dr.  McClintic  in  every 
way,"  asserted  the  board  president,  William  Treacy,  "and  if  necessary 
fire  this  man  Cooley."^^ 

The  battle  between  Cooley  and  Tuttle,  which  was  peppered  with 
rumors  of  wildly  intemperate  remarks  by  both  men,  spilled  over  to 
the  federal  level  when  the  Montana  State  Board  of  Health  appealed 
to  the  U.S.  Public  Health  and  Marine  Hospital  Service  and  Cooley 
appealed  to  the  U.S.  Bureau  of  Entomology  to  clarify  jurisdiction  in 
spotted  fever  work.  L.  O.  Howard,  chief  of  the  U.S.  Bureau  of  En- 
tomology, contacted  Surgeon  General  Walter  Wyman,  but  to  no  avail. 
Commenting  to  Cooley  that  he  had  run  "up  against  a  stone  wall," 


Tick  Eradication  Efforts,  ipii-i^zo 


83 


Buildings  in  Victor,  Montana,  used  as  a  laboratory  by  Thomas  B.  McClintic 
and  Lunsford  D.  Fricks  of  the  U.S.  Public  Health  Service  from 
(Courtesy  of  the  Rocky  Mountain  Laboratories,  NIAID.) 

Howard  observ^ed  that  the  U.S.  Public  Health  and  Marine  Hospital 
Service  saw  "no  necessity  for  any  cooperation  whatever"  and  appar- 
ently felt  "perfectly  competent  to  handle  the  whole  matter."^^  Having 
successfully  employed  insect  and  rodent  control  measures  to  suppress 
other  arthropod-borne  diseases,  the  Service  doubtless  believed  that  its 
officers  had  sufficient  expertise  to  oversee  the  dipping  of  livestock  and 
the  destruction  of  small  rodents  in  Montana.  Moreover,  since  all  of- 
ficers were  physicians,  they  could  also  employ  bacteriological  tech- 
niques in  the  study  of  the  disease  organism  itself  and  offer  medical 
assistance  to  the  victims  of  spotted  fever.  As  a  result  of  this  federal- 
level  interchange,  the  U.S.  Bureau  of  Entomology  withdrew  its  support 
from  Cooley's  work  at  the  end  of  the  19 11  season.  The  animosity- 
generated  by  the  episode,  however,  remained. 

While  this  political  storm  raged  around  him,  Thomas  B.  McCHntic 
initiated  his  own  spotted  fever  research.  Using  funds  appropriated  by 
the  Montana  state  legislature,  McClintic  hoped  to  test  the  feasibility 
of  eradicating  the  tick  in  infected  territories,  to  continue  Ricketts's 
w^ork  of  testing  the  susceptibilit)-  of  the  wild  mammals  to  experimental 
inoculation  with  spotted  fever,  and  to  search  for  the  infection  among 
the  wild  mammals  in  nature.  McClintic  worked  in  a  heavily  infected 


84 


Rocky  Mountain  Spotted  Fever 


district  near  Victor  bounded  on  the  north  by  Sweathouse  Creek  and 
on  the  south  by  Bear  Creek.  This  was  the  territory  in  which  Ricketts 
had  found  infected  ticks  in  nature,  and  which,  because  of  the  presence 
of  the  disease,  had  become  almost  depopulated.^^ 

Because  McClintic  did  not  arrive  until  the  latter  part  of  May,  it  was 
quite  late  in  the  season  to  begin  the  work.  Nonetheless,  he  determined 
to  proceed,  hoping  to  continue  the  work  on  a  broader  scale  the  fol- 
lowing year.  In  his  plan  for  tick  eradication,  McClintic  rejected  the 
idea  that  dipping  alone  would  accomplish  tick  eradication  in  the  Bit- 
terroot,  because,  he  said,  "both  in  point  of  numbers  and  variety  of 
species  the  fauna  of  the  valley  is  excelled  by  very  few  other  localities 
of  similar  size  in  the  United  States,  and  most  of  the  mammals,  both 
wild  and  domestic,  harbor  the  tick  in  one  form  or  another."^"^ 

McClintic  oversaw  construction  of  a  $520  concrete  vat  for  dipping 
livestock,  which  was  made  according  to  plans  published  by  the  De- 
partment of  Agriculture  and  was  similar  to  the  vat  used  in  Florence 
by  the  U.S.  Bureau  of  Entomology.  Nine  feet  deep,  about  five  feet  wide, 
and  thirty-eight  feet  long  at  the  water  line,  it  was  filled  with  approx- 
imately twenty-five  hundred  gallons  of  arsenical  dipping  fluid  to  a 
depth  of  five  and  one-half  feet.  This  sufficed  to  immerse  all  stock, 
except  for  exceptionally  large  horses. Arriving  at  the  vat,  stock  were 
herded  into  a  corral  and  then  driven  individually  up  a  ramp  and  onto 
a  boiler-metal  slide  that  sloped  downward  into  the  vat  itself.  After 
immersion,  the  stock  were  dried  in  dripping  pens  before  being  returned 
to  pasture. 

Because  corralling  and  driving  the  stock  into  the  vat  could  be  dif- 
ficult, a  seasoned  stock  handler  was  essential.  During  the  farmers'  busy 
season,  moreover,  yet  another  person  was  needed  to  bring  stock  in 
from  the  surrounding  farms.  Most  stock  owners  cooperated,  McClintic 
observed,  but  a  few,  "as  is  usually  the  case  in  undertakings  in  the 
interest  of  the  public  health,"  objected  to  having  anything  done  that 
caused  "any  inconvenience  or  work."  By  the  middle  of  June  the  vat 
was  completed,  and  dipping  began  under  the  supervision  of  McClintic 
and  his  assistant  William  Colby  Rucker,  who  had  recently  arrived. 
Initially,  116  horses,  199  cattle,  and  108  sheep  were  dipped.  Two 
weeks  later,  on  3  July,  redipping  was  begun,  but  "as  the  stock  .  .  . 
was  found  to  be  practically  free  from  ticks,"  only  38  horses,  57  cattle, 
and  60  sheep  were  dipped  again.^^ 

In  addition  to  the  dipping  program  and  recommendations  for  clear- 
ing and  cultivation  of  land,  McCHntic  and  Rucker  launched  a  campaign 
to  destroy  the  wild  mammals  on  which  the  immature  stages  of  the 
tick  fed.  The  pine  squirrel,  yellow-bellied  chipmunk,  wood  rat,  wood- 


Tick  Eradication  Efforts,  ipii-ipzo 


8S 


chuck,  weasel,  and  badger  were  all  targeted  in  this  program,  but  the 
local  ground  squirrel,  Citellus  columbianus,  was  believed  to  be  by  far 
the  most  significant  pest  in  the  valley.  Of  3,465  animals  shot  or  trapped 
during  the  191 1  season,  3,233  were  ground  squirrels.  An  uncounted 
number  of  other  animals  were  killed  with  poisoned  oats  or  with  carbon 
bisulphide  placed  in  their  burrows,  a  method  employed  successfully 
against  ground  squirrels  in  the  Service's  antiplague  campaign  in  Cal- 
ifornia.^^ 

McClintic  and  Rucker  concluded  their  work  in  early  August  and 
moved  their  laboratory  studies  back  to  the  Hygienic  Laboratory  in 
Washington,  D.C.  With  the  191 2  election  approaching,  they  found 
politics  as  well  as  the  weather  heating  up  in  the  nation's  capital.  To 
the  Democrats'  delight,  the  spUt  between  President  William  Howard 
Taft  and  his  predecessor  Theodore  Roosevelt  was  polarizing  the  Re- 
publican party.  McChntic  and  Rucker's  own  agency  was  likewise  em- 
broiled in  a  political  battle.  A  bill  was  before  Congress  to  expand  the 
authority  of  the  U.S.  Pubhc  Health  and  Marine  Hospital  Service,  but 
another  bill  proposed  to  create  a  wholly  separate  department  of  public 
health.  Surgeon  General  Wyman  was  busily  promoting  the  Service's 
bill  and  maneuvering  to  thwart  those  who  would  challenge  his  agency's 
hegemony  in  the  federal  bureaucracy.^^ 

In  November  the  sixty-three-year-old  Wyman  died  suddenly.  Having 
served  as  surgeon  general  for  twenty  years,  he  was  the  only  leader 
many  Service  officers  could  remember.  McClintic  interrupted  his  re- 
search to  accompany  Wyman's  body  to  Saint  Louis  for  burial.  Iron- 
ically, Wyman's  death  breathed  new  life  into  a  scaled-down  version 
of  his  Service  reform  legislation.  By  the  time  McClintic  and  Rucker 
left  for  Montana  in  the  spring  of  19 1 2,  another  bill  was  moving  through 
Congress  that  proposed  to  shorten  the  name  of  the  Service  to  the  U.S. 
Public  Health  Service  and  to  broaden  its  authority  to  conduct  re- 
search. 

During  the  fall  and  winter  of  1911-12,  McClintic  tested  a  number 
of  drugs  for  their  therapeutic  properties  against  spotted  fever.  This 
work,  which  resulted  in  negative  findings,  will  be  examined  more 
closely  in  chapter  10.  The  spring  of  19 12  held  great  promise  for 
McClintic,  both  personally  and  professionally.  On  2  March  he  married 
Theresa  Drexel,  and  the  following  day  the  couple  left  for  Montana  to 
combine  a  honeymoon  in  the  Bitterroot  Valley  with  spotted  fever 
research.'^^  McClintic  and  Rucker  continued  the  work  begun  in  191 1, 
dipping  livestock  and  kiUing  small  mammals.  Their  laboratory  ex- 
periments were  designed  to  study  the  natural  history  of  the  disease, 
the  important  work  Ricketts  had  planned  before  his  death  from  typhus. 


86 


Rocky  Mountain  Spotted  Fever 


The  natural  history  experiments  were  tedious.  Ground  squirrels  and 
most  other  small  mammals  showed  no  identifiable  illness,  hence  an 
indirect  method  had  to  be  employed.  McClintic  and  Rucker  would 
inoculate  a  wild  animal  with  spotted  fever,  and  after  five  days  its  blood 
was  injected  into  a  guinea  pig.  Another  waiting  period  followed,  during 
which  the  guinea  pig  was  observed  for  symptoms  of  the  disease.  If  it 
became  ill,  the  original  animal  was  judged  to  be  susceptible  to  exper- 
imental inoculation  with  spotted  fever.  If  the  guinea  pig  remained  well, 
a  final  test  was  made  by  inoculating  it  with  virulent  spotted  fever 
blood.  If  the  guinea  pig  again  remained  healthy,  the  experiment  was 
inconclusive  because  it  was  judged  to  have  been  immune  to  spotted 
fever  from  the  outset.  If  the  guinea  pig  succumbed,  however,  the  orig- 
inal mammal  was  declared  to  have  acquired  immunity  from  an  earlier 
infection  in  nature. 

By  this  time-consuming  method,  McClintic  determined  that,  in  ad- 
dition to  ground  squirrels,  weasels,  woodchucks,  and  mountain  goats 
were  susceptible  to  the  disease.  Many  other  animals  were  tested  with 
negative  results.  Badgers,  for  example,  could  be  experimentally  in- 
fected, but  infection  was  slight  and  infrequent.  Since  the  spotted  fever 
tick  had  never  been  observed  feeding  on  a  badger,  moreover,  the  animal 
could  practically  be  eliminated  as  a  potential  reservoir  in  nature. 

Locating  immune  ground  squirrels  in  nature  was  one  key  to  iden- 
tifying them  as  a  significant  mammalian  reservoir  of  the  disease.  During 
the  191 1  season,  McClintic  had  experimented  with  21  ground  squirrels 
from  the  heavily  infected  Victor  area,  but  the  results  were  inconclusive. 
In  19 1 2  he  expanded  the  experiments,  using  194  ground  squirrels.  Of 
these,  34  again  gave  questionable  results  and  had  to  be  discarded. 
Among  the  160  remaining  ground  squirrels,  McClintic  found  40  to 
be  naturally  immune.  When  the  ground  squirrels  were  grouped  ac- 
cording to  the  locality  from  which  they  were  collected,  a  higher  per- 
centage of  immune  squirrels  was  found  in  highly  infected  spotted  fever 
areas."^^ 

Another  major  line  of  research  focused  on  a  large-scale  study  of 
infective  ticks  in  nature.  McClintic  collected  nearly  2,000  ticks  from 
different  localities  in  the  Bitterroot  and  from  Bannock  County,  Idaho. 
His  results  were  similar  to  those  obtained  by  Ricketts,  but,  because 
of  the  large  scale  on  which  they  had  been  conducted,  they  established 
more  conclusively  that  infected  ticks  did  indeed  exist  in  nature. "^"^ 

Early  in  August,  McClintic  completed  the  season's  work  and  pre- 
pared his  laboratory  experiments  once  more  for  transfer  to  the  Hygienic 
Laboratory.  On  9  August,  however.  Service  headquarters  in  Washing- 
ton, D.C.,  received  a  wire  from  Thomas  D.  Turtle  that  McCHntic  was 


Tick  Eradication  Efforts,  ipii-ipzo 


87 


In  1911  and  1912  Thomas  B. 
McClintic  of  the  U.S.  PubUc 
Health  and  Marine  Hospital  Ser- 
vice continued  Howard  Taylor 
Ricketts's  studies  of  spotted  fe- 
ver in  nature,  providing  more 
conclusive  proof  of  Ricketts's 
tentative  results.  Near  the  end 
of  his  work  in  19 12,  McClintic 
became  infected  with  spotted 
fever  and  died— the  first  of 
many  laboratory  investigators 
who  lost  their  lives  in  the  study 
of  the  deadly  disease.  In  19 14 
the  U.S.  Congress  recognized 
McClintic's  death  in  the  line  of 
duty  with  a  private  act.  (Cour- 
tesy of  the  National  Library  of 
Medicine.) 


ill  with  an  undiagnosed  disease  but  proceeding  east  by  train,  where 
he  planned  to  join  his  wife,  who  had  returned  earlier.  By  the  time  the 
train  reached  Chicago,  it  was  clear  to  Karl  H.  Kellogg,  a  Stevensville 
physician  who  accompanied  McClintic,  that  the  young  investigator 
had  fallen  victim  to  spotted  fever.  Determined  to  return  home,  however, 
McClintic  rebuffed  an  offer  of  medical  care  in  Chicago.  Before  the 
train  reached  Baltimore,  McClintic  had  lost  consciousness,  and  he  died 
at  Georgetown  University  Hospital  on  13  August  19 12,  the  evening 
of  his  arrival  and  the  day  before  President  Taft  signed  the  act  that 
shortened  the  Service's  name  to  U.S.  Public  Health  Service.  In  19 14 
the  U.S.  Congress  recognized  McClintic's  service  and  death  in  the  line 
of  duty  in  a  private  act.  It  provided  a  lump  sum  award  of  $5,760  — 
an  amount  equal  to  two  years'  pay  and  allowances— to  Theresa  Drexel 
McClintic,  who  never  remarried. 

Spotted  fever  had  claimed  its  first  victim  among  the  researchers  who 
probed  its  mysteries.  McClintic's  death  cast  the  dangers  of  research 
in  bold  relief,  but  according  to  a  newspaper  in  Washington,  D.C.,  there 
was  no  question  that  the  work  would  be  resumed.  Rupert  Blue,  the 
new  surgeon  general  of  the  renamed  U.S.  Public  Health  Service,  chose 
Lunsford  Dickson  Pricks  to  replace  McClintic  in  spotted  fever  work."^^ 
The  son  of  a  physician  in  Rising  Fawn,  Georgia,  Pricks  was  born  on 


88 


Rocky  Mountain  Spotted  Fever 


From  1913  to  191 7,  Lunsford  D. 
Fricks  supervised  the  U.S.  Public 
Health  Service  program  to  rid 
the  Bitterroot  Valley  of  spotted 
fever.  His  proposals  clashed  with 
those  supported  by  the  Montana 
State  Board  of  Entomology. 
(Courtesy  of  the  National 
Library  of  Medicine.) 


18  July  1873.  After  graduating  first  in  the  1897  class  of  the  Chatta- 
nooga (Tennessee)  Medical  College,  he  joined  the  Service  as  an  intern 
and  by  19 13  had  progressed  through  the  ranks  to  Surgeon.  During 
the  Spanish-American  War,  Fricks  monitored  U.S.  troops  to  prevent 
the  introduction  of  yellow  fever  into  the  United  States.  While  on  quar- 
antine duty  two  years  later,  he  suffered  a  bout  with  the  infamous 
Yellow  Jack.  From  his  medical  school  days,  Fricks  had  been  interested 
in  microscopical  investigations.  Like  McCHntic  before  him,  Fricks  ar- 
rived in  Montana,  in  the  spring  of  191 3,  only  to  be  surprised  by  new 
political  developments  relating  to  spotted  fever. 

When  the  U.S.  Bureau  of  Entomology  had  withdrawn  from  spotted 
fever  work,  Robert  A.  Cooley  had  been  unable  to  continue  his  own 
tick  eradication  efforts.  Taking  a  new  approach,  Cooley  proposed  to 
F.  B.  Linfield,  director  of  the  Montana  agricultural  experiment  station, 
that  a  state  entomological  commission  be  established  to  supervise  tick 
eradication  work  in  the  Bitterroot.  Linfield  concurred  and  suggested 
that  the  board  be  comprised  of  Cooley  as  state  entomologist,  Tuttle 
as  secretary  of  the  state  board  of  health,  and— to  serve  as  a  buffer 


Tick  Eradication  Efforts,  ipii-ipzo 


89 


between  the  two  strong-willed  men— W.  J.  Butler,  the  state  veterinar- 
ian. State  Senator  Fred  Whiteside  agreed  to  sponsor  the  bill  in  the 
19 1 3  session  of  the  Montana  state  legislature.  Working  with  Whiteside, 
Cooley  ensured  that  the  bill  was  broadly  worded,  allowing  the  board 
to  investigate  other  disease-carrying  insects  as  well  as  the  spotted  fever 
tick.  The  new  board  was  needed,  Cooley  stated,  because  there  existed 
no  official  state  agency  "clothed  with  all  the  legal  authority  needed  to 
prescribe  and  enforce  the  necessary  rules  and  regulations"  for  the 
eradication  of  the  spotted  fever  tick.  Approved  on  18  March  191 3, 
the  new  law  authorized  a  Montana  State  Board  of  Entomology  to 
"take  steps  to  eradicate  and  prevent  the  spread  of  Rocky  Mountain 
tick  fever.  Infantile  Paralysis  and  all  other  infections  of  communicable 
diseases  that  may  be  transmitted  or  carried  by  insects. '"^^ 

Smooth  functioning  of  the  new  state  board  was  fostered  by  the 
resignation  of  Thomas  D.  Tuttle  as  secretary  of  the  Montana  State 
Board  of  Health.  His  term  ended  in  December  19 12,  and  when  Gov- 
ernor Samuel  V.  Stewart  offered  him  a  position  as  first  director  of  the 
Montana  Tuberculosis  Sanatorium,  he  accepted.  For  all  of  his  efforts 
on  behalf  of  pubUc  health,  including  a  state  food  and  drug  law  as  well 
as  the  sanitorium,  the  Montana  Medical  Association  awarded  Tuttle 
its  first  Ricketts  Memorial  Medal,  established  to  honor  the  revered 
research  martyr."^^  Tuttle  appeared  happy  to  escape  the  continual  bat- 
tles with  Cooley,  which,  he  noted,  had  contributed  to  a  chronic  stomach 
ulcer.  As  his  successor  he  recommended  WiUiam  Forlong  Cogswell,  a 
physician  in  Livingston,  Montana,  and  a  Canadian  native  trained  at 
Dalhousie  University  Medical  School  in  Halifax,  Nova  Scotia. Cogs- 
well was  duly  elected  at  a  special  meeting  of  the  state  board  of  health 
on  16  December.  Fearing  that  Cogswell  would  continue  Tuttle's  pol- 
icies, Cooley  did  not  initially  inform  him  about  the  proposed  board 
of  entomology  law.  Linfield,  however,  actively  lobbied  Cogswell  and 
succeeded  in  persuading  him  to  testify  in  favor  of  the  bill's  passage.^^ 

At  the  first  meeting  of  the  Montana  State  Board  of  Entomology,  a 
defensive  Cooley  recommended  that  the  U.S.  Bureau  of  Entomology, 
which  had  recently  received  a  fifteen-thousand-dollar  appropriation 
for  use  in  spotted  fever  tick  eradication,  be  given  exclusive  rights  to 
the  tick  eradication  work,  thus  shutting  the  U.S.  Public  Health  Service 
out  of  any  involvement.  The  two  other  board  members,  Cogswell  and 
the  state  veterinarian,  W.  J.  Butler,  however,  consulted  with  Governor 
Stewart  and  formulated  a  plan  by  which  more  harmonious  relations 
might  be  maintained  between  the  state  and  the  two  federal  agencies. 
Their  proposal,  carried  over  Cooley's  objection,  called  for  a  conference 
with  representatives  of  the  two  federal  agencies  to  work  out  an  ac- 


90 


Rocky  Mountain  Spotted  Fever 


ceptable  compromise.  At  the  meeting,  held  ii  April  19 13,  W.  D. 
Hunter  of  the  U.S.  Bureau  of  Entomology  and  Lunsford  D.  Pricks  of 
the  U.S.  Public  Health  Service  agreed  to  divide  tick  control  w^ork  in 
the  Bitterroot  Valley  geographically.  A  line  of  division  w^as  set  at  Big 
Creek,  southw^est  of  Stevensville.  Territory  north  of  this  line  was  de- 
clared the  province  of  the  U.S.  Bureau  of  Entomology,  w^ith  Cooley 
in  charge  of  the  w^ork.  The  southern  part  of  the  valley  w^ould  be  under 
the  jurisdiction  of  Fricks,  representing  the  U.S.  PubHc  Health  Service. 
On  instructions  from  Service  headquarters,  however,  Fricks  was  to 
report  only  to  the  secretary  of  the  Montana  State  Board  of  Health.^^ 

To  residents  of  the  Bitterroot,  this  division  must  have  seemed  pe- 
culiar, especially  since  each  agency  advocated  different  measures  to 
rid  the  valley  of  its  scourge.  Initially  the  entomologists  stood  fast  by 
their  contention  that  within  two  or  three  years  livestock  dipping  alone 
would  reduce  the  spotted  fever  tick  to  levels  such  that  the  disease 
would  no  longer  be  a  threat.  Destruction  of  the  small  rodents  that 
harbored  the  immature  stages  of  the  tick  was  described  only  as  "an 
important  secondary  means  of  combating  the  tick."  In  contrast,  Fricks, 
representing  the  medical  position,  held  that  a  vigorously  prosecuted, 
three-pronged  program  was  necessary.  Of  equal  importance  to  live- 
stock dipping,  Fricks  argued,  was  an  active  campaign  to  destroy  small 
rodents.  In  addition,  he  insisted  that  legislation  should  be  passed  re- 
stricting domestic  stock  from  grazing  on  the  infected  west  side  of  the 
river  during  tick  season.  In  spite  of  these  differences,  the  Northwest 
Tribune  reported  the  conference  as  the  beginning  of  a  concerted  war 
on  the  wood  tick,  never  mentioning  spotted  fever.^^ 

These  different  approaches  led  to  a  second  conference  on  18  July. 
Cooley  argued  that  the  division  of  responsibility  was  not  proving 
effective.  Fricks  caused  dissension,  Cooley  alleged,  by  claiming  that 
"dipping  would  not  get  rid  of  the  tick  in  thirty  years."  Cooley  further 
asserted  that  Fricks  did  "not  know  any  more  about  entomology"  than 
Cooley  did  about  medicine.  Cooley's  plan  was  to  divide  the  work 
along  professional  speciaHzations:  the  U.S.  Bureau  of  Entomology 
should  solely  manage  tick  control  operations;  the  U.S.  Public  Health 
Service,  laboratory  experiments;  and  the  U.S.  Bureau  of  Biological 
Survey,  which  Cooley  hoped  would  reactivate  its  participation,  ground 
squirrel  eradication.^^ 

Believing  that  it  was  "not  fitting"  for  two  federal  agencies  to  "haggle 
with  the  state  authorities"  over  the  work,  Fricks  recommended  to 
Surgeon  General  Blue  that  the  U.S.  Public  Health  Service  withdraw 
from  tick  control  work  entirely.  L.  O.  Howard,  chief  of  the  U.S.  Bureau 
of  Entomology,  Hkewise  suggested  to  Blue  that  the  bureau's  generous 


Tick  Eradication  Efforts,  1911-1910 


91 


appropriation  for  tick  eradication  work  would  surely  be  renewed  and 
would  provide  ample  funds  for  the  work.  Howard  argued  that  "perfect 
harmony"  could  be  achieved  if  the  Service  did  pathological  work  and 
left  tick  eradication  to  the  entomologists/"^ 

At  U.S.  Pubhc  Health  Service  headquarters,  reaction  to  this  new 
proposal  was  uniformly  negative.  Service  leaders  had  battled  since  the 
1870s  for  primacy  in  federal  health  matters,  and  they  were  not  inclined 
to  yield  any  of  their  hard-won  authority.  Blue  notified  Howard  that 
the  Service  intended  to  continue  its  work  and  remarked  that  the  sur- 
render of  functions  was  hardly  cooperation,  "at  least  in  the  best  sense 
of  the  term."  In  a  memo  to  his  superior.  Secretary  of  the  Treasury 
WiUiam  G.  McAdoo,  Blue  reiterated  the  Service's  longstanding  position 
that  spotted  fever,  in  all  its  aspects,  was  essentially  a  public  health 
problem.  "It  would  be  as  logical,"  Blue  wrote,  "to  turn  over  to  the 
Bureau  of  Entomology  the  suppression  of  yellow  fever  epidemics,  be- 
cause the  disease  is  spread  by  mosquitoes."  If  such  a  precedent  were 
set,  "it  would  also  be  necessary  to  turn  over  to  the  Bureau  of  Animal 
Industry  the  dipping  of  cattle  because  several  domestic  animals  harbor 
the  tick,  [and]  also  a  part  of  this  work  would  have  to  be  given  to  the 
Forestry  Service  because  ticks  are  found  in  the  Forest  Reserves  bor- 
dering the  Bitter  Root  Valley."^^  Fricks,  furthermore,  was  advised  to 
revise  his  position,  letting  it  be  known  that  the  Service  would  not 
withdraw  "without  a  fight."  Observing  that  Cooley  would  probably 
attempt  to  "slip  the  skids  under  you  at  the  first  opportunity,"  Blue 
cautioned  Fricks,  "Whatever  you  do,  don't  let  any  of  them  back  you 
out  of  there."^^ 

For  five  years,  from  19 13  through  19 17,  two  federal  agencies  ad- 
vocating two  separate  programs  combated  a  tick  known  by  two  names. 
Since  the  dipping  of  livestock  was  the  most  visible  aspect  of  both 
agencies'  efforts  — and  the  one  most  directly  affecting  the  livelihood  of 
valley  residents— any  problem  with  this  undertaking  jeopardized  the 
future  of  the  entire  program.  Unfortunately,  the  mild  dipping  solution 
available  on  the  open  market,  which  contained  0.169  percent  of  ar- 
senious  oxide,  proved  to  be  too  weak  to  kill  engorged  female  ticks. 
When  the  strength  was  increased  to  0.228  percent— the  concentration 
commonly  used  throughout  the  south  to  treat  Texas  cattle  fever— the 
solution  burned  the  hides  of  Montana  cattle.  As  the  search  continued 
for  an  acceptable  concentration,  other  quality  control  problems  de- 
veloped. On  one  occasion,  for  example,  the  kerosene  and  water  in  the 
dip  separated  when  it  was  allowed  to  stand  unused  for  several  hours. 
When  cattle  were  subsequently  immersed,  the  solution  burned  the 
cows'  udders.^^ 


92 


Rocky  Mountain  Spotted  Fever 


An  arsenical  solution  killed  ticks  on  the  hides  of  livestock  in  the  fifteen 
seconds  it  took  to  swim  through  the  concrete  dipping  vat.  Rocky  Mountain 
wood  ticks,  however,  preferred  to  attach  themselves  around  the  horns  and 
ears  of  cattle.  It  was  nearly  impossible  to  submerge  the  heads  of  the  cattle 
for  longer  than  one  second,  which  was  insufficient  time  to  do  serious  harm 
to  engorged  female  ticks.  (Courtesy  of  the  National  Archives  and  Records 
Administration.) 


These  difficulties,  which  might  be  expected  in  any  new  undertaking, 
generated  significant  ill-feeling  in  the  owners  of  the  afflicted  stock. 
Local  ranchers,  who  remained  skeptical  of  the  tick  theory  and  who, 
during  tick  season,  blamed  the  dip  for  any  sickness  or  death  among 
their  stock,  filed  several  lawsuits.  The  state  attorney  general  exacer- 
bated already  strained  relations  when  he  ruled  that  the  state  was  not 
hable  for  accidental  death  or  damage  to  the  ranchers'  stock  caused  by 
the  program. By  19 14  a  less  damaging  arsenic  dip  was  identified, 
but  Bitterroot  Valley  ranchers  who  sustained  real  or  imaginary  losses 
from  the  dipping  procedure  were  not  inclined  to  be  patient.^^ 


Tick  Eradication  Efforts,  ipii-ipzo 


93 


In  June  19 13  the  U.S.  Public  Health  Service's  vat  at  Hamilton  was 
destroyed  by  vandalism,  and  later  that  month  the  U.S.  Bureau  of 
Entomology's  vat  at  Florence  was  dynamited.  No  precipitating  incident 
was  traced  to  the  Hamilton  attack.  In  Florence,  however,  Carl  and 
George  Wemple,  brothers  aged  nine  and  eleven  who  assisted  at  the 
vat  on  their  family's  property,  had  fallen  ill  with  spotted  fever.  After 
George  died,  the  vat  was  destroyed. ^°  During  his  investigation  of  the 
incident,  Cooley  was  advised  that  the  people  of  Florence,  whom  he 
termed  in  exasperation  "an  ignorant,  mean  lot,"  felt  no  remorse  over 
the  dynamited  vat.  In  fact,  since  many  of  them  rejected  the  tick  trans- 
mission theory  outright,  there  existed  "quite  a  hard  feeling  among 
them"  about  the  dipping  program.  In  response  to  the  incidents,  the 
Montana  State  Board  of  Entomology  called  for  vigorous  prosecution 
of  anyone  vandalizing  the  dipping  vats.  The  board  also  increased  its 
educational  efforts  among  ranchers,  utilizing  circulars  and  demon- 
strations. Within  a  year  the  board  reported  that  public  attitude  in  the 
Stevensville  and  Florence  districts  had  been  so  changed  that  it  was  no 
longer  necessary  to  argue  the  question  of  tick  transmission  of  spotted 
fever.  Residents  of  the  Lo  Lo  canyon  area  remained  unconvinced  and 
never  installed  a  vat,  but  they  refrained  from  taking  violent  action 
against  other  facilities  in  the  program.^^ 

To  determine  the  relative  extent  of  tick  infestation  in  different  sec- 
tions of  the  Bitterroot  and  to  serve  as  a  check  upon  the  efficacy  of  tick 
eradication  measures,  Willard  V.  King  and  Lunsford  D.  Fricks  con- 
ducted tick  surveys  in  their  respective  control  districts.  King  examined 
livestock  for  tick  infestation  in  the  U.S.  Bureau  of  Entomology's  dis- 
tricts; Fricks  undertook  a  more  ambitious  survey,  gathering  ticks  from 
the  riverbank,  from  the  rolling  benchlands,  and  even  from  the  high 
reaches  of  the  Bitterroot  Mountains.  He  found  practically  no  ticks  on 
the  cultivated  lands,  a  zone  of  heavy  infestation  in  the  hills  where 
horses  and  cattle  were  allowed  to  range,  a  zone  of  "moderate"  infes- 
tation—up to  7,040  ticks  per  square  mile— just  above  the  range  of 
domestic  animals,  and,  finally,  an  extraordinarily  heavy  infestation, 
estimated  at  millions  of  ticks  per  square  mile,  in  "goat  country,"  the 
high  mountainous  area  where  large  numbers  of  Rocky  Mountain  goats 
ranged.  Because  heavy  infestations  at  the  higher  elevations  constantly 
threatened  the  tick  eradication  efforts  in  the  valley,  Fricks  concluded 
that  ultimate  success  would  depend  upon  "the  creation  of  a  tick-free 
zone  extending  as  far  as  possible  up  into  the  Bitter  Root  Mountains. "^^ 

Both  groups  also  took  a  census  of  livestock  in  the  valley.  Surprisingly, 
it  revealed  that  relatively  few  animals  ranged  over  the  tick-infested 
areas.  In  the  Victor  district,  for  example,  there  were  1,865  animals, 


94 


Rocky  Mountain  Spotted  Fever 


but  only  350  cattle  and  50  horses  required  regular  dipping.  The  re- 
maining 1,500  animals  were  either  pastured  on  the  tick-free  bottom- 
lands or  classified  as  dairy  cows  or  work  horses,  animals  exempted 
from  dipping  if  their  owners  agreed  to  remove  ticks  by  hand.^^ 

Since  there  were  so  few  animals  that  actually  needed  to  be  dipped, 
Fricks  strongly  recommended  that  the  grazing  of  livestock  be  restricted 
by  law  during  the  spring.  "It  would  be  cheaper,"  he  noted,  "to  prohibit 
such  grazing  entirely  than  to  construct  and  operate  dipping  vats."  The 
Montana  State  Board  of  Entomology,  however,  consistently  refused 
to  adopt  restrictions,  arguing  that  they  would  generate  hostihty  among 
the  citizenry.  After  one  meeting  at  which  restrictions  were  considered 
and  soundly  defeated,  Cooley  wrote  to  King  that  "each  member  of 
the  board,  speaking  for  himself,  said  that  he  did  not  care  to  take  the 
responsibility  of  voting  such  a  regulation  through. "^"^ 

Fricks  also  maintained  that  the  labor  costs  of  ground  squirrel  erad- 
ication, viewed  by  Cooley  as  excessively  expensive,  could  be  controlled 
by  inducing  landowners  themselves  to  do  the  work.  To  this  end  he 
procured  twelve  "squirrel  destroyers,"  or  carbon  bisulphide  pumps, 
like  those  used  by  the  Service  in  the  antiplague  campaign  on  the  Pacific 
coast.  Farmers  were  offered  free  use  of  the  pump  for  a  specified  pe- 
riod.^^ 

In  addition,  Fricks  suggested  the  novel  idea  that  west  side  landowners 
substitute  bands  of  sheep  for  their  horses  and  cattle.  Sheep  had  been 
grazed  closely  on  the  east  side  of  the  valley  since  about  1890,  Fricks 
noted,  and  tick  infestation  there  was  practically  nonexistent.  He  con- 
cluded that  sheep  grazing  might  be  an  economical  method  to  rid  the 
west  side  of  ticks  as  well.  It  was  known,  moreover,  that  lanolin  in 
sheep  wool  was  repugnant  to  ticks  and  that  the  density  of  the  wool 
made  it  difficult  for  male  and  female  ticks  to  locate  one  another  for 
mating.  In  an  experiment  Fricks  conducted  during  19 13  with  one  small 
band  of  sheep,  over  87  percent  of  295  ticks  placed  in  the  wool  of 
unshorn  sheep  were  recovered  dead.  Moreover,  most  ticks  recovered 
from  sheep  grazing  naturally  were  found  dead,  and  many  engorged 
females  appeared  to  be  unfertilized.^^ 

More  importantly,  sheep  were  known  to  eat  the  brush  vegetation 
in  which  ticks  dwelled.  By  herding  them  back  toward  the  foothills  as 
they  grazed,  Fricks  argued,  a  habitat  alien  to  the  tick  would  be  pro- 
duced. Other  large  domestic  and  wild  animals  would  be  removed  from 
sheep  ranges,  and  some  ticks  would  be  destroyed  simply  by  the  grazing 
of  sheep.  Finally,  Fricks  observed  that  if  further  experiments  with  sheep 
proved  successful,  tick  eradication  could  be  placed  on  an  industrial 


Tick  Eradication  Efforts,  ipii-ipzo 


95 


basis.  This  would  significantly  diminish  the  cost  of  spotted  fever  control 
work  to  the  federal  and  Montana  taxpayers. 

The  chilly  reception  given  to  Fricks's  theory  by  Cooley  and  King 
reflected  the  ongoing  tension  between  the  U.S.  Public  Health  Service 
and  the  Montana  State  Board  of  Entomology.  At  Cooley's  request, 
King  repeated  Fricks's  experiment  with  a  band  of  six  sheep.  His  findings 
indicated  that  "the  number  of  ticks  which  developed  on  the  sheep 
were  more  than  sufficient  to  maintain  a  normal  supply."  King  did  not 
explore  whether  sheep  grazing  might  control  the  underbrush  that  har- 
bored ticks.  To  Cooley,  King  wrote  that  "only  in  a  special  combination 
of  circumstances  can  sheep  be  relied  upon  to  effect  reduction  of  the 
tick."  He  did  not  elaborate  on  what  these  circumstances  were  or 
whether  they  existed  in  the  Bitterroot.^^ 

Because  Fricks's  plan  remained  experimental  and  was  never  sup- 
ported on  a  wide  scale,  moreover,  it  is  difficult  to  assess  its  potential 
merits.  Initially  there  was  optimism  among  Bitterroot  residents,  and 
some  ranchers  added  sheep  to  their  stock. Had  the  plan  proved 
efficacious,  of  course,  it  would  have  merited  praise  for  cost-effective- 
ness. Under  the  strained  circumstances,  no  adequate  trial  was  ever 
conducted. 

By  19 1 6  experience  had  demonstrated  that  rodent  control  and  graz- 
ing restrictions  would  indeed  be  necessary  if  the  Rocky  Mountain  wood 
tick  was  to  be  eliminated  from  the  Bitterroot  Valley.  The  "starvation" 
method  used  so  successfully  against  the  Texas  cattle  fever  tick,  Mar- 
garopus  annulatus,  simply  did  not  work  in  Montana.  That  tick  spent 
its  entire  life  cycle  on  one  animal,  hence  dipping  killed  all  stages.  The 
spotted  fever  tick,  in  contrast,  fed  on  different  animals  in  the  larval, 
nymphal,  and  adult  stages.  The  Texas  cattle  fever  tick  died  after  one 
year  if  unable  to  reach  a  host,  but  the  hardier  Rocky  Mountain  wood 
tick  could  remain  unfed  for  three  years  or  longer,  after  which  it  would 
feed  and  reproduce  if  placed  on  a  host.^° 

Furthermore,  Montana's  climate  interfered  with  dipping  operations 
during  the  crucial  early  spring  period.  "One  warm  sunshiny  day  in 
March  is  sufficient  to  bring  forth  the  adult  ticks,"  Fricks  wrote  after 
one  season  in  Montana,  "and  when  this  is  followed  by  a  week  or  more 
of  freezing  weather  .  .  .  during  which  it  is  impossible  to  use  the  dip, 
some  females  may  be  fertilized  and  drop  off  for  egg  laying  before  it 
is  possible  to  destroy  them."  CompHcating  this  situation  further  was 
the  tick's  predilection  for  attaching  itself  to  cattle  "around  the  horns, 
ears,  and  high  up  on  the  neck."  The  average  time  required  by  a  cow 
to  swim  through  the  Victor  vat  was  found  to  be  fifteen  seconds,  and 


96 


Rocky  Mountain  Spotted  Fever 


all  ticks  submerged  that  length  of  time  were  killed  or  incapacitated. 
The  cattle,  however,  swam  with  their  heads  out  of  the  solution.  It  was 
almost  impossible  to  submerge  them  completely  for  longer  than  one 
second,  a  period  insufficient  to  do  serious  harm  to  the  engorged  females 
in  any  strength  that  could  be  borne  by  the  livestock. 

The  entire  spotted  fever  situation  changed  "materially"  in  the  spring 
of  19 1 5,  when  the  disease  was  reported  from  eastern  Montana.  "To 
the  surprise  of  us  all,"  Cooley  noted,  two  cases  appeared  in  the  northern 
part  of  Gallatin  County,  near  Bozeman,  and  a  few  were  reported  near 
Billings.  "Something  hke  ten  or  a  dozen"  cases  were  reported  from 
the  flat,  sagebrush  country  in  eastern  Montana  near  Miles  City  and 
others  from  Richland  County,  which  bordered  North  Dakota.^^  Of 
thirty-five  cases  reported  in  19 15,  only  seven  occurred  in  the  Bitterroot 
Valley  and  Missoula  areas,  while  twenty-three  were  reported  from  the 
newly  discovered  eastern  areas  of  infection.  The  disease  seemed  to 
take  the  mild  Idaho  form  in  the  eastern  counties,  for  only  two  deaths 
were  reported,  compared  with  five  among  the  Bitterroot  Valley  cases. 
W.  F.  Cogswell,  secretary  of  the  Montana  State  Board  of  Health,  told 
the  press  that  spotted  fever  had  probably  spread  into  eastern  Montana 
from  Wyoming.  "The  new  cases  are  occurring  along  the  Powder  river, 
which  has  its  source  in  Wyoming."^^ 

Both  the  U.S.  Public  Health  Service  and  the  Montana  State  Board 
of  Entomology  launched  investigations  of  this  new  appearance  of  spot- 
ted fever.  The  Service  had  detailed  a  young  assistant  surgeon,  Roscoe 
Roy  Spencer,  to  assist  Fricks  in  1915;  Fricks  sent  Spencer  to  Miles 
City,  Montana,  to  confirm  the  diagnosis  of  spotted  fever  by  inoculating 
guinea  pigs  with  the  blood  of  patients. The  Montana  State  Board  of 
Entomology  focused  on  the  ecology  of  eastern  Montana  spotted  fever. 
Cooley  assigned  the  project  to  Ralph  Robinson  Parker,  a  young  as- 
sistant entomologist  employed  by  the  state  board.  Ten  years  later,  these 
two  "R.R.s,"  as  they  were  often  called,  would  collaborate  on  a  vaccine 
against  spotted  fever,  but  at  the  end  of  the  summer  of  19 15,  Spencer 
returned  to  his  rotating  assignments  as  a  new  Service  officer.  Parker, 
on  the  other  hand,  continued  to  be  intimately  involved  with  spotted 
fever  control  work. 

The  twenty-seven-year-old  son  of  a  Massachusetts  physician,  Parker 
was  a  graduate  student  in  entomology  at  Cooley's  alma  mater,  the 
Massachusetts  Agricultural  College. In  19 14,  Cooley  had  written  to 
his  mentor  H.  T.  Fernald,  seeking  the  name  of  a  student  who  might 
be  interested  in  studying  flies  and  their  relation  to  typhoid  fever  for 
the  Montana  State  Board  of  Entomology.  Fernald  recommended 
Parker,  and  Cooley  recruited  him  to  work  during  that  summer  in  the 


Tick  Eradication  Efforts,  i^ii-i^zo 


97 


Yellowstone  valley.  An  extremely  conscientious  worker  and  meticulous 
record  keeper,  Parker  surveyed  the  eastern  Montana  spotted  fever 
situation  in  19 15  and  returned  in  19 16  with  his  Ph.D.  in  hand  to 
establish  a  field  station  at  Powderville,  Montana.  With  the  assistance 
of  his  bride,  Adah  Nicolet  Parker,  the  young  entomologist  investigated 
topography  and  vegetation  in  addition  to  the  local  species  of  ticks  and 
their  animal  hosts.  His  most  disturbing  finding  was  that  in  this  area, 
small  animals,  particularly  rabbits,  served  as  hosts  to  adult  as  well  as 
immature  stages  of  the  tick.  Dipping  domestic  stock  would  be  futile 
if  adult  ticks  matured  on  the  widely  distributed  rabbits.  The  following 
year  Parker  gathered  additional  information  in  Musselshell,  Montana, 
but  he  offered  no  concrete  suggestions  for  tick  control. 

As  it  became  manifest  that  spotted  fever  would  not  be  eradicated 
as  simply  and  quickly  as  had  Texas  cattle  fever,  the  Montana  State 
Board  of  Entomology  reluctantly  adopted  a  regulation  restricting,  with 
some  exceptions,  the  grazing  of  livestock  in  the  Bitterroot  Valley  be- 
tween I  March  and  15  July  each  year.  Ground  squirrel  destruction 
also  became  a  more  important  part  of  the  U.S.  Bureau  of  Entomology's 
control  program.  In  the  fall  of  19 16  a  newspaper  article  reported  on 
the  expanded  control  program  with  no  mention  that  the  U.S.  Public 
Health  Service  had  advocated  such  methods  since  191 1.  Fricks  reacted 
to  this  article  as  Tuttle  had  before  him:  the  entomologists,  he  believed, 
were  claiming  credit  that  rightly  belonged  to  others.  Fricks  protested 
the  perceived  injustice,  but  the  entomologists  maintained  that  they  had 
come  to  their  conclusions  independently.^'' 

More  substantive  was  an  ongoing  disagreement  between  Fricks  and 
the  Montana  State  Board  of  Entomology  over  grazing  restrictions.  The 
board's  regulations  authorized  exemptions  for  persons  who  grazed 
their  stock  on  state  land  under  long-term  leases.  The  state  was  loath 
to  cancel  these  leases,  even  though  many  of  the  lessees  were  absentee 
owners,  and  the  Montana  State  Board  of  Entomology  argued  for  the 
exemptions  on  the  grounds  that  some  of  the  lessees  had  few  other 
means  of  income.  Fricks  countered  that  this  argument  was  wholly 
unacceptable.  "By  the  same  reasoning,  many  practices,  such  as  piracy 
and  highway  robbery  for  instance,  which  are  now  under  the  ban  of 
the  law  might  easily  be  condoned. "^^ 

In  December  19 16,  Fricks  appealed  to  federal  officials  in  Washington 
to  put  pressure  on  the  state  authorities.  William  P.  Malburn,  writing 
for  the  secretary  of  the  treasury,  accordingly  reminded  Governor  Sam- 
uel V.  Stewart  of  the  "large  sums  of  money  which  this  Department 
has  expended  in  the  endeavor  to  control  this  disease  in  the  State  of 
Montana."  He  urged  state  authorities  to  adopt  strict  grazing  restric- 


98 


Rocky  Mountain  Spotted  Fever 


tions  immediately.  The  state  board  of  health  secretary,  W.  F.  Cogswell, 
replied  to  this  letter,  explaining  the  exceptions,  but  Treasury  Secretary 
William  G.  McAdoo  was  not  appeased.  Reiterating  the  federal  financial 
investment,  McAdoo  warned  that  the  state  must  enact  and  enforce 
more  stringent  grazing  restrictions  if  the  work  of  the  U.S.  Public  Health 
Service  was  to  be  continued. 

Even  as  this  exchange  was  occurring,  the  United  States  was  being 
pulled  relentlessly  into  World  War  I.  President  Woodrow  Wilson  had 
been  reelected  on  the  slogan  "He  Kept  Us  out  of  War,"  but  a  German 
declaration  of  unrestricted  submarine  warfare  in  January  19 17,  fol- 
lowed by  the  actual  torpedoing  of  several  ships,  induced  Wilson  to 
change  his  position.  By  6  April  19 17  both  houses  of  Congress  had 
voted  to  declare  war.  The  following  day,  at  a  meeting  of  the  Montana 
State  Board  of  Entomology,  Fricks  took  the  first  step  toward  disen- 
gaging the  U.S.  Pubhc  Health  Service  from  its  commitment  in  Montana. 
He  introduced  a  resolution  declaring  a  portion  of  the  territory  on  the 
west  side  of  the  Bitterroot  tick  free.  In  his  report  of  this  meeting  to 
the  surgeon  general,  Fricks  noted  that  Willard  V.  King  had  admitted 
"for  the  first  time,  that  the  dipping  of  domestic  animals  had  proven 
impracticable  as  a  tick  eradicative  measure  in  the  Bitter  Root  Valley." 
Furthermore,  he  continued,  "the  Board  passed  a  resolution  favoring 
the  introduction  of  sheep  for  this  purpose."  Fricks  recommended  that 
the  Service  discontinue  its  work  after  30  June  19 17,  since  its  position 
had  been  "vindicated."  Surgeon  General  Blue  concurred  and  informed 
Cogswell  that  the  Service  was  withdrawing.  Fricks,  who  had  grown 
to  love  the  Bitterroot  Valley,  was  ordered  to  Memphis,  Tennessee,  to 
take  charge  of  malaria  control  work  for  the  duration  of  the  war.^° 

After  the  withdrawal  of  the  U.S.  Public  Health  Service,  the  state 
board  of  entomology  voted  unanimously  to  ask  the  U.S.  Bureau  of 
Entomology  to  take  over  control  work  for  the  entire  valley.  Cooley 
wrote  to  Congresswoman  Jeanette  Rankin,  whose  father  had  died  of 
spotted  fever  in  1904,  for  assistance  in  securing  a  larger  appropriation 
for  the  work.  The  U.S.  Bureau  of  Entomology,  however,  had  changed 
its  mind  about  participating.  "The  matter  primarily  is  a  question  of 
public  health,"  stated  the  secretary  of  agriculture  in  his  reply  to  Ran- 
kin's inquiry.  "It  is  believed  that  the  question  of  eradication  is  one 
which  should  be  dealt  with  by  the  State  authorities  and,  if  the  assistance 
of  the  Federal  Government  is  needed,  the  cooperation  of  the  Health 
Service  should  be  sought.  While  the  Bureau  of  Entomology  heretofore 
has  done  some  work  in  connection  with  the  eradication  of  the  disease, 
it  seems  advisable  hereafter  for  that  Bureau  to  deal  only  with  the 
entomological  phases  of  the  problem,  such  as  the  study  of  the  fife 


Tick  Eradication  Efforts,  i^ii—i^io 


99 


history  and  habits  of  the  tick  and  similar  matters. "^^ 

The  absence  of  any  federal  assistance  left  Montana  in  a  financially 
difficult  position.  The  state  board  of  entomology  resolved  to  continue 
the  work  and  in  the  spring  of  191 8  appointed  Ralph  R.  Parker  to  take 
charge  of  control  measures  in  the  Bitterroot.  During  the  previous  fall, 
Parker  had  spent  two  months  at  Harvard  University  in  productive 
research  on  the  anatomy  of  ticks  and  was  clearly  the  most  knowl- 
edgeable entomologist  available  to  Montana  authorities.  He  worked 
with  little  money  and  few^  assistants,  since  many  young  men  had  vol- 
unteered for  service  in  the  military.  The  vats  at  Stevensville  and  Blodgett 
Creek  leaked,  the  Victor  vat  needed  repairs,  and  there  was  a  problem 
getting  water  to  the  Florence  vat.  Local  committees,  however,  sup- 
ported Parker,  advocating  enforced  dipping  and  expressing  willingness 
to  assume  a  larger  share  of  the  cost.^^ 

After  directing  the  control  program  for  only  a  short  time,  Parker 
concluded  that  its  priorities  needed  to  be  reordered.  "I  am  seriously 
of  the  opinion,"  he  wTote  to  Cooley,  "that  the  work  here  will  have  to 
undergo  a  radical  change  ...  if  we  are  to  get  real  results.  Frankly  I 
am  in  favor  of  cutting  out  the  dipping  absolutely.  I  have  no  faith  in 
it."  He  pointed  out  that  Montana's  cold  spring  made  dipping  impos- 
sible during  late  February  and  early  March.  "It  seems  to  me  that  under 
the  best  of  conditions  ...  we  cannot,  by  dipping  get  more  than  a  scant 
25%  of  the  ticks  that  actually  engorge  on  the  animals."  He  concluded 
that  ground  squirrel  control  coupled  with  restrictions  on  grazing  con- 
stituted a  better  approach. 

The  entire  program,  moreover,  was  under  some  strain  during  this 
period.  In  spite  of  five  years  of  tick  control  efforts,  spotted  fever  had 
not  been  eradicated.  There  continued  to  be  some  opposition  from  some 
stock  owners  to  grazing  restrictions,  and  the  game  warden  opposed 
the  "indiscriminate"  use  of  poisoned  grain  because  of  the  hazard  it 
posed  to  birds.  In  support  of  the  program,  Cooley  argued  that  spotted 
fever  cases  had  been  reduced  from  eleven  to  three  from  1913  to  1918. 
King  published  data  indicating  that  the  number  of  ticks  had  been 
reduced  80—90  percent,  although  he  noted  that  the  reduction  varied 
from  area  to  area.  Given  this  unsettled  situation,  Cooley  soHcited 
testimonial  letters  from  valley  residents  for  the  board's  third  biennial 
report,  presumably  to  buttress  the  board's  appropriation  request.^"^ 

Although  Montana  lawmakers  did  increase  the  budget  of  the  board 
for  1919  and  1920,  they  curtailed  the  appropriation  in  1921.^^'  Cooley 
and  Parker  had  hoped  to  launch  a  broad-scale  study  of  spotted  fever 
in  nature  as  a  basis  for  developing  more  efficient  and  permanent  meth- 
ods to  destroy  the  tick.  In  1920,  furthermore,  Cooley  recommended 


lOO 


Rocky  Mountain  Spotted  Fever 


that  tick  control  operations  be  extended  into  the  mountainous  regions, 
including  possible  extermination  of  the  Rocky  Mountain  goat,  which 
had  been  shown  to  serve  as  a  major  natural  host  for  adult  ticks.  A 
few  years  later,  this  proposition  became  a  minor  cause  celebre  as 
wildlife  lovers  came  to  the  goat's  defense.  The  author  of  a  Northwest 
Tribune  article  entitled  "The  Mountain  Goat  or  Taxpayers  Goat" 
argued  that  the  entire  tick  control  program  was  a  sink  for  money  and 
had  produced  scant  results.  Unless  it  could  be  shown  definitively  that 
the  program  was  effective,  "a  pause  should  be  made  before  continuing 
to  throw  money  into  the  bottomless  well."^^ 

The  reduced  appropriation  in  192 1  ironically  coincided  with  a  pre- 
cipitous rise  in  the  number  of  spotted  fever  cases  in  the  Bitterroot— 
from  four  in  1920  to  eleven  in  1921.  All  eleven  cases,  moreover,  proved 
fatal.  Among  the  victims  were  two  prominent  Lo  Lo  residents,  Mon- 
tana State  Senator  Tyler  Worden  and  his  wife,  who  was  president  of 
the  Montana  Federation  of  Women's  Clubs.  All  but  two  of  the  1921 
cases  were  acquired  in  the  canyons  running  back  into  the  Bitterroot 
Mountains,  which  indicated  that  although  the  tick  control  program 
had  contributed  to  the  safety  of  residents  within  the  control  districts, 
spotted  fever  remained  a  hazard  in  the  valley.  Worried  state  officials, 
fearing  that  the  disease  might  be  in  a  resurgence,  petitioned  the  U.S. 
Public  Health  Service  to  return. 

A  decade  of  tick  control  efforts  had  reduced  the  tick  population  but 
had  not  succeeded  in  ridding  the  Bitterroot  of  spotted  fever.  In  assessing 
the  work  of  this  period,  it  is  necessary  to  recall  that  in  19 10,  when 
the  hope  for  a  medical  approach  to  spotted  fever  control  seemed  to 
die  with  Howard  Taylor  Ricketts,  vector  control  offered  the  most 
promising  method  of  combating  the  disease.  Similar  efforts  against 
yellow  fever  and  Texas  cattle  fever  had  produced  stunning  results,  and 
doubtless  Robert  A.  Cooley  and  his  associates  hoped  to  rid  western 
Montana  of  its  scourge  with  the  same  simple,  effective  measures.  Cool- 
ey's  personal  clash  with  Thomas  D.  Tuttle,  unfortunately,  led  the 
ambitious  entomologist  into  a  combatant  posture  with  the  U.S.  PubHc 
Health  Service  that  surely  retarded  adoption  of  control  methods  other 
than  livestock  dipping.  The  insistence  of  the  Service  that  its  officers 
deal  only  with  the  state  health  officer  rather  than  with  the  Montana 
State  Board  of  Entomology,  moreover,  exacerbated  the  situation.  In 
retrospect,  these  quarrels  may  have  cost  Montana  and  federal  taxpayers 
additional  money,  but  at  that  time  the  control  efforts  themselves  ap- 
peared to  be  the  only  recourse  available  by  which  virulent  spotted 
fever  in  the  Bitterroot  could  be  attacked,  and  thus  they  provided  a 
means  for  some  type  of  active  response  against  the  deadly  affliction. 


Chapter  Six 


A  Wholly  New  Type 
of  Microorganism 

Nature  makes  so  gradual  a  transition  from  the  inanimate  to  the  animate 
kingdom  that  the  boundary  lines  which  separate  them  are  indistinct  and 
doubtful. 

Aristotle,  Historia  Animalium 


From  1902,  when  Louis  B.  Wilson  and  William  M.  Chowning 
launched  the  first  scientific  investigation,  until  19 10,  when  Howard 
Taylor  Ricketts  died,  bacteriological  techniques  had  been  the  methods 
of  choice  among  investigators  of  Rocky  Mountain  spotted  fever.  Using 
the  microscope,  blood  smears,  staining  and  fixing  techniques,  and 
animal  inoculations,  bacteriologists  had  demonstrated  tick  transmis- 
sion and  identified  a  suspected  organism.  Conclusive  proof  that  this 
microorganism  caused  spotted  fever  eluded  early  researchers,  however, 
because  they  could  not  cultivate  the  organism  on  artificial  media,  a 
requirement  laid  down  by  Robert  Koch  to  demonstrate  bacterial  cau- 
sation.^ Serum  therapy  used  successfully  against  some  other  diseases, 
furthermore,  had  failed  to  produce  a  dramatic  cure  for  spotted  fever, 
and,  in  any  case,  efforts  to  develop  preventive  or  therapeutic  medical 
strategies  had  died  with  Ricketts.  With  the  armamentarium  of  bac- 
teriology so  depleted,  investigators  sought  new  approaches  to  identify 
spotted  fever's  mysterious  etiological  agent.  During  the  second  pro- 
ductive period  of  laboratory  research  on  spotted  fever,  the  methods 
of  pathology  supplanted  those  of  bacteriology  in  unraveUng  this  por- 
tion of  the  riddle. 

The  beginning  of  systematic  study  in  disease  pathology  is  usually 
traced  to  the  work  of  Giovanni  Battista  Morgagni,  an  eighteenth- 
century  professor  of  anatomy  at  the  University  of  Padua.  Morgagni 
noted  particular  lesions  found  at  autopsy  and  suggested  that  they  might 
explain  clinical  symptoms.  His  observations  stimulated  a  systematized 
search  to  correlate  pathological  lesions  with  symptoms.  By  the  mid 


lOI 


I02 


Rocky  Mountain  Spotted  Fever 


nineteenth  century,  sufficient  data  had  been  gathered  to  distinguish 
among  many  diseases  with  similar  characteristics.  With  improvements 
to  the  microscope  after  1830,  it  became  possible  to  study  the  fine 
structures  of  the  body.  In  1858,  building  on  concurrent  discoveries 
that  plant  and  animal  tissues  w^ere  comprised  of  cells,  Rudolf  Virchow^ 
postulated  the  doctrine  of  cellular  pathology  — that  disease  occurred 
because  of  interaction  between  living  cells  and  disease  agents.  After 
1880,  when  the  light  microscope  was  perfected  and  the  discovery  of 
bacteria  stimulated  the  development  of  staining  methods  and  other 
techniques,  careful  studies  of  the  cellular  pathology— or  histology,  as 
it  came  to  be  called— of  diseased  tissue  became  possible. 

Since  the  most  pressing  need  during  the  early  decades  of  histological 
study  was  information  about  such  major  infectious  diseases  as  tuber- 
culosis and  typhoid  fever,  rare  maladies  such  as  Rocky  Mountain 
spotted  fever  received  httle  attention.  Aside  from  Wilson  and  Chown- 
ing's  autopsy  notations  on  gross  pathology,  E.  R.  LeCount,  an  associate 
of  Ricketts  at  Rush  Medical  College  in  Chicago,  had  by  19 16  produced 
the  sole  histological  study  of  spotted  fever.  LeCount's  work  was  not 
exhaustive  but  rather  constituted  the  initial  findings  of  a  larger  study 
abruptly  terminated  by  Ricketts's  death.  The  microscopic  changes 
caused  by  spotted  fever  infection,  LeCount  noted,  were  of  two  sorts. 
First,  diffuse  lesions,  affecting  entire  groups  of  organs,  were  similar  to 
the  changes  caused  by  other  infectious  diseases.  Second  and  more 
important,  he  believed,  were  the  "focal  lesions"  connected  with  the 
occlusion  of  blood  vessels  in  sections  of  the  skin,  liver,  kidney,  spleen, 
and  adrenal  glands.  Although  LeCount  also  found  capillaries  and  small 
veins  in  the  lung  and  heart  practically  occluded  with  leukocytes,  he 
concluded  that  "there  were  no  serious  consequences  of  these  conditions 
with  exception  of  minute  hemorrhages  beneath  the  endocardium." 
Likening  the  changes  caused  by  excessive  leukocytes  and  the  focal 
lesions  to  those  seen  in  typhoid  fever,  LeCount  speculated  that  they 
were  probably  caused  by  the  "action  of  the  toxin  of  this  disease." 
Some  of  the  "so-called  'endothelial  toxins'  "  he  noted,  were  believed 
to  be  "Hberated  from  the  bodies  of  bacteria."^ 

In  January  191 6,  Simeon  Burt  Wolbach,  a  pathologist  at  Harvard 
University  School  of  Medicine,  became  interested  in  Rocky  Mountain 
spotted  fever.  Trained  under  the  distinguished  pathologists  William  T. 
Councilman  and  Frank  B.  Mallory,  Wolbach  had  in  191 1  participated 
in  studies  of  trypanosomiasis,  parasitic  protozoa,  and  tropical  ulcers 
in  Gambia,  then  a  British  colony,  on  the  west  coast  of  Africa.^  The 
publications  resulting  from  this  work  earned  Wolbach  promotions  at 
Harvard,  to  associate  professor  of  bacteriology  in  19 14  and  to  associate 


A  Wholly  New  Type  of  Microorganism 


103 


professor  of  pathology  two  years  later.  Wolbach  began  his  work  with 
strains  of  spotted  fever  obtained  from  Surgeon  Lunsford  D.  Fricks  of 
the  U.S.  Public  Health  Service,  who  was  continuing  his  own  bacteri- 
ological studies  in  addition  to  implementing  tick  control  efforts.^ 

About  the  same  time,  Hideyo  Noguchi,  a  bacteriologist  at  the  Rock- 
efeller Institute  for  Medical  Research  in  New  York  also  entered  spotted 
fever  investigations.^  Having  achieved  prestigious  status  as  a  full  mem- 
ber of  the  Rockefeller  Institute  in  19 14,  Noguchi  was  well  known  for 
his  early  work  on  snake  venoms  and  his  more  recent  work  on  spi- 
rochetes, especially  on  Treponema  pallidum,  the  cause  of  syphilis. 
According  to  Noguchi's  biographer,  Isabel  R.  Plesset,  Noguchi  cast 
about  during  191 5  for  an  interesting  new  problem  and  selected  Rocky 
Mountain  spotted  fever,  which  resembled  his  homeland's  tsutsuga- 
mushi  disease.  In  late  191 5  or  early  19 16,  Noguchi  visited  Fricks  at 
the  Hygienic  Laboratory  and  obtained  strains  of  spotted  fever  in  guinea 
pigs.  The  entrance  of  this  more  senior,  celebrated  Rockefeller  re- 
searcher into  the  spotted  fever  field  prodded  both  Wolbach  and  Fricks 
to  speed  up  their  work.^ 

Fricks,  who  had  already  studied  spotted  fever  for  three  years,  has- 
tened to  pubhsh  the  results  of  his  microscopical  research.  In  early 
19 1 6,  at  medical  meetings  in  Missoula  and  Salt  Lake  City,  Fricks 
announced  that  he  had  consistently  found  "extra  corpuscular  granules" 
in  the  blood  of  human  and  animal  victims  of  spotted  fever.  These,  he 
stated,  occurred  singly  and  in  pairs  and,  when  stained  by  the  Giemsa 
method,  appeared  bright  red  and  were  highly  refractile.  He  also  found 
similar  bodies  "within  or  in  close  proximity  to"  the  red  blood  cells. 
Those  inside  the  red  cell,  he  said,  were  "round  or  slightly  elongated 
red  chromatin  bodies  partially  surrounded  by  or  in  close  approxi- 
mation to  a  somewhat  larger  deep-blue  staining  body."  All  of  the 
chromatin  bodies  were  one  micron  or  less  in  diameter.  Fricks  concluded 
that  the  "morphological  and  tinctorial  characteristics"  of  these  bodies 
implied  that  they  were  of  a  protozoan  nature.^ 

Wolbach,  although  just  beginning  his  studies,  had  little  regard  for 
Fricks's  presumed  organism.  Corresponding  with  the  secretary  of  the 
Montana  State  Board  of  Health,  W.  F.  Cogswell,  Wolbach  confided, 
"I  am  on  an  entirely  different  track  and  have  great  hopes  of  contributing 
something  of  importance."  It  would  take  time,  he  continued,  to  confirm 
his  hypotheses,  because  he  was  using  the  "peculiarly  difficult  tech- 
nique" of  teasing  apart  tick  tissues  rather  than  crushing  them.  Initially, 
Wolbach  had  planned  to  supplement  these  laboratory  studies  of  tick 
and  guinea  pig  tissues  by  travefing  to  Montana  to  study  human  cases 
of  the  disease,  and  to  this  end  he  had  requested  that  the  Montana 


I04 


Rocky  Mountain  Spotted  Fever 


S.  Burt  Wolbach,  a  pathologist  at  Harvard  University  School  of  Medicine, 
described  spotted  fever  as  an  infection  of  the  circulatory  system  and  identi- 
fied the  causative  organism  in  the  tissues  of  infected  ticks,  experimental  ani- 
mals, and  human  victims.  Wolbach  also  recognized  that  the  rickettsial 
organisms  could  not  be  cultured  on  lifeless  media  but  required  living  cells 
in  which  to  grow  and  replicate.  (Courtesy  of  the  National  Library  of 
Medicine.) 


State  Board  of  Entomology  detail  Ralph  R.  Parker  to  assist  him.  Robert 
A.  Cooley,  however,  wanted  Parker  to  spend  the  summer  in  Powderville 
studying  Eastern  Montana  spotted  fever,  just  recognized  the  previous 
year.  All  hope  of  studying  human  cases  evaporated  when  Wolbach 
suffered  an  attack  of  appendicitis  with  compUcations  that  precluded 
any  travel.^ 

Despite  this  setback,  Wolbach  determined  to  pubHsh  preHminary 
findings  based  solely  on  studies  of  tick  and  guinea  pig  tissues  rather 
than  risk  losing  priority  to  Noguchi.^  His  research  had  revealed,  Wol- 
bach wrote  to  Cooley,  that  spotted  fever  affected  "primarily  the  pe- 
ripheral blood  vessels"  and  that  the  rash  and  necrosis  were  "secondary 
to  the  vascular  lesions."  These  findings  were  "entirely  consistent  and 
confirmatory  of  clinical  descriptions  of  the  disease,"  he  continued,  and 
he  expressed  surprise  that  no  one  had  previously  paid  attention  to  the 
tissues,  which  he  regarded  as  essential. 

In  mid  191 6,  Wolbach  published  two  papers  on  these  preliminary 
findings  in  the  Journal  of  Medical  Research.  In  the  first  he  described 
a  Gram-negative  organism  from  0.2  to  0.5  microns  wide  that  occa- 


A  Wholly  New  Type  of  Microorganism 


105 


sionally  occurred  "in  large  numbers"  and  was  concentrated  in  the 
"smooth  muscle  cells  of  affected  arteries  and  veins."  With  Giemsa's 
stain  the  organisms  stained  "bluish,"  this  being  "in  marked  contrast 
to  most  bacteria,  which  take  an  intense  reddish  purple  stain."  Since 
this  reddish  purple  coloration  — usually  achieved  by  using  the  Ro- 
manowsky  stain— was  regarded  as  the  chromatin  staining  reaction, 
Wolbach  noted  that  he  was  "somewhat  at  a  loss  to  understand  the 
description  'chromatin  staining'  by  Ricketts  as  applied  to  this  orga- 
nism." This  initial  paper  was  followed  a  few  months  later  by  a  second 
preliminary  report  on  the  organism  in  ticks.  Although  he  had  observed 
the  organism  throughout  tick  tissues,  Wolbach  concluded  that  there 
was  no  cellular  reaction  in  the  ticks  to  the  presence  of  the  parasites, 
"even  when  present  in  enormous  numbers."  This  was  indicative  that 
the  organism  had  evolved  a  symbiotic  relationship  with  its  tick  host 
over  centuries. 

Ironically,  although  it  was  Noguchi's  perceived  competition  that 
stimulated  the  publication  of  Fricks's  and  Wolbach's  papers,  Noguchi 
himself  did  not  make  much  progress  during  19 16  on  spotted  fever. 
His  attention  had  turned  instead  to  studies  of  the  spirochete  that  caused 
Weil's  disease,  an  organism  that  he  identified  as  a  new  genus,  Lep- 
tospira. Having  read  the  papers  published  by  both  Fricks  and  Wolbach, 
Noguchi  was  inclined  to  support  Fricks's  protozoan  theory.  When  he 
received  a  slide  of  Fricks's  presumed  organism,  Noguchi  replied  that 
he,  too,  had  "seen  similar  bodies  several  times"  in  his  own  work.  It 
is  not  surprising  that  Noguchi,  as  a  speciahst  in  spirochetes,  some  of 
which  were  known  to  be  arthropod-borne,  was  receptive  to  the  pos- 
sibihty  of  a  spotted  fever  organism  with  protozoan  characteristics.^^ 

Smarting  under  Noguchi's  preference  for  Fricks's  protozoan  theory, 
Wolbach  characterized  Noguchi  and  his  colleagues  as  "the  skeptical 
autocrats  at  the  Rockefeller  Institute." Such  feelings  of  institutional 
rivalry  also  emerged  at  the  Hygienic  Laboratory.  The  director,  George 
W.  McCoy,  wrote  encouragingly  to  Fricks  that  no  one  at  the  laboratory 
was  concerned  about  Wolbach's  publication.  They  had  concluded  that 
Wolbach's  organism  was  probably  the  same  organism  Fricks  had  seen. 
"Unless  Noguchi  has  something  a  whole  lot  better  than  Wolbach," 
McCoy  continued,  "we  should  worry."  He  noted  that  the  laboratory's 
histologist  had  thus  far  been  unable  to  verify  Wolbach's  findings  of 
the  organism  in  tissues.  Furthermore,  Arthur  M.  Stimson,  another 
researcher  at  the  laboratory  and  later  director  of  its  Division  of  Sci- 
entific Research,  was  attempting  to  duplicate  and  verify  Fricks's  re- 
search. Unfortunately,  McCoy  informed  Fricks,  although  Stimson  had 
seen  the  "intracorpuscular  bugs"  once  under  the  microscope,  he  had 


io6 


Rocky  Mountain  Spotted  Fever 


"not  been  able  to  find  them  since  to  show  us."  McCoy  remained 
confident,  however,  that  Fricks's  work  would  soon  be  confirmed. 

It  was,  however,  the  pathological  approach  of  Wolbach  that  would 
reveal  definitively  the  etiology  of  spotted  fever.  As  he  continued  his 
examination  of  guinea  pig  lesions  and  tick  tissues,  an  entirely  unan- 
ticipated phenomenon  altered  Wolbach's  perception  of  the  nature  of 
the  disease  organism.  By  December  191 6  he  was  certain  that  he  had 
seen  the  organism  multiplying  "in  the  nuclei  of  the  Malpighian  tubules 
of  ticks.  This  is  the  first  instance  known,"  he  wrote  to  Cooley,  "of  a 
parasite  multiplying  inside  of  nuclei.  As  you  see,  I  am  getting  away 
from  the  idea  that  the  organism  is  a  bacterium." 

In  the  spring  of  19 17,  Wolbach  was  finally  able  come  to  Montana 
for  several  weeks,  where  he  conducted  two  autopsies  on  spotted  fever 
victims.  To  his  surprise,  the  lesions  of  the  disease  in  humans  had  an 
"exact  similarity"  to  those  in  animals.  Commenting  on  this  "remark- 
able feature,"  of  spotted  fever,  Wolbach  asserted,  "There  is  probably 
no  other  disease  of  man  which  is  so  accurately  duplicated  in  animals." 

In  19 1 8,  Wolbach  published  a  third  preliminary  report,  this  one  on 
spotted  fever  in  humans.  In  this  paper,  and  in  his  report  to  the  chairmen 
of  the  Montana  state  boards  of  health  and  entomology,  Wolbach  stated 
emphatically,  "It  is  possible  now  to  define  Rocky  Mountain  Spotted 
Fever  as  a  disease  of  the  peripheral  blood  vessels,  a  specific  endangiitis 
caused  by  the  minute  parasite  described  in  my  first  report."  Moreover, 
Wolbach  had  decided  that  the  spotted  fever  organism  was  indeed 
unique.  "My  opinion  regarding  the  organism,"  he  wrote  Cooley,  "is 
that  it  represents  a  wholly  new  type  of  micro-organism  and  that  it 
probably  stands  intermediate  between  the  bacteria  and  protozoa  as 
does  spirochaeta."^^ 

Because  of  this  intellectually  exciting  discovery,  Wolbach  hoped  to 
launch  a  large-scale  research  project  on  spotted  fever  at  Harvard.  He 
invited  Ralph  R.  Parker,  who  had  investigated  tick  anatomy  at  Harvard 
for  a  brief  period  in  19 17,  to  assist  with  entomological  studies  for 
"one  or  two  years"  under  a  special  grant  from  the  university  — an  offer 
that  appeared  hard  to  turn  down  in  Parker's  mind.  World  War  I  and 
the  19 1 8  influenza  pandemic,  however,  thwarted  these  plans.  Wolbach 
dropped  spotted  fever  work  for  a  time  in  order  to  study  influenza.  He 
wrote  to  Cooley:  "Some  day  and  as  soon  as  possible  we  shall  see  an 
adequately  organized  research  on  Spotted  Fever;  but  that  can  not  be 
until  the  war  is  over.  We  are  stripped  to  the  last  man  here  and  the 
calls  for  men  are  so  urgent  that  it  will  be  impossible  to  put  through 
my  intention  now."^^ 

During  that  tumultuous  summer,  a  tragedy  in  Noguchi's  laboratory 


A  Wholly  New  Type  of  Microorganism 


107 


at  the  Rockefeller  Institute  helped  to  confirm  that  Wolbach's  organism 
was  indeed  the  cause  of  spotted  fever.  Noguchi  had  been  hospitalized 
in  May  19 17  with  typhoid  fever  and  had  suffered  relapses  that  pre- 
vented his  return  to  the  laboratory  for  nearly  a  year.  During  his  absence, 
all  of  Noguchi's  cultures  were  maintained  by  his  laboratory  assistant, 
twenty-three-year-old  Stephen  Mohnscek.  Shortly  after  Noguchi's  re- 
turn to  the  laboratory  in  March  19 18,  Molinscek  fell  ill.  Noguchi  later 
contended  that  Molinscek  had  scratched  his  hand  or  arm  with  a  needle, 
but  Molinscek  told  his  attending  physician  that  he  could  not  remember 
any  laboratory  accident.  On  18  March,  Molinscek  was  hospitalized 
after  developing  symptoms  that  were  provisionally  diagnosed  as  Brill's 
disease,  spotted  fever,  or  possibly  typhoid. ^° 

Noguchi  himself  cultured  Molinscek's  blood  to  rule  out  a  laboratory 
spirochetal  infection.  Typhoid  was  also  eliminated  after  several  Widal 
tests  gave  negative  results.  When  Molinscek  died  a  week  later,  however, 
the  diagnosis  was  still  uncertain.  Samples  of  Molinscek's  tissues  were 
sent  to  Wolbach  at  Harvard  for  examination,  and  he  confirmed  typical 
spotted  fever  organisms  in  the  vascular  lesions.  Guinea  pigs  inoculated 
with  Molinscek's  blood  showed  characteristic  spotted  fever  signs, 
hence  the  attending  physician  concluded  that  spotted  fever  had  been 
the  cause. 

By  accepting  Wolbach's  diagnosis  of  Molinscek's  terminal  illness, 
the  Rockefeller  Institute  in  effect  confirmed  Wolbach's  research.  Fol- 
lowing this  incident,  the  Harvard  pathologist  prepared  a  definitive 
paper  on  Rocky  Mountain  spotted  fever  that  occupied  the  entire  197 
pages  of  the  November  19 19  issue  of  the  Journal  of  Medical  Research. 
In  addition  to  presenting  an  exhaustive  review  of  the  Hterature,  clinical 
observations,  epidemiological  evidence,  an  analysis  of  the  Hfe  cycle  of 
the  tick  vector,  and  a  detailed  description  of  his  histological  method, 
Wolbach  expanded  his  discussion  of  the  differences  he  had  observed 
between  the  spotted  fever  organism  and  bacteria.  He  particularly  em- 
phasized the  fact  that  the  organism  invaded  the  nuclei  of  tick  cells, 
often  "completely  filling  and  even  distending  the  nucleus."  Noting  his 
early  reluctance  to  accept  the  intranuclear  bodies  as  forms  of  the 
spotted  fever  organism,  Wolbach  emphasized  that  he  now  regarded 
them  "as  the  most  characteristic  form  in  infected  ticks."  He  reiterated, 
moreover,  that  this  phenomenon  was  the  impetus  for  concluding  that 
the  agent  of  spotted  fever  indeed  represented  "a  new  form  of  micro- 
organism." He  proposed  that  it  be  called  Dermacentroxenus  rickettsi, 
taking  the  genus  name  from  the  tick  known  to  carry  the  disease  and 
choosing  the  species  name  "in  honor  of  Ricketts  who  first  saw  it  in 
the  blood."^^ 


io8 


Rocky  Mountain  Spotted  Fever 


S.  Burt  Wolbach's  drawing  of  the 
spotted  fever  organism  in  the 
tissues  of  infected  animals. 
Wolbach's  name  for  the  organism, 
Dermacentroxenus  rickettsi,  was 
later  supplanted  by  the  currently 
accepted  designation,  Rickettsia 
rickettsii.  (Reproduced  from  S.  Burt 
Wolbach,  "Studies  on  Rocky 
Mountain  Spotted  Fever,"  Journal 
of  Medical  Research  41  [19 19]: 
1-197.) 

Wolbach  did  not  accept  Ricketts's  description  of  nonpathogenic 
organisms  in  the  eggs  of  uninfected  ticks.  Robert  A.  Cooley  prepared 
slides  of  noninfective  tick  eggs  for  Wolbach  and  identified  short  rods 
as  identical  with  those  that  Ricketts  had  described.  These  short  rods, 
Wolbach  maintained,  were  not  the  spotted  fever  organism,  which  in 
tick  eggs  exhibited  a  lanceolate  form.  Ricketts  had  been  misled,  Wol- 
bach concluded,  by  having  the  "misfortune"  to  work  with  ticks  con- 
taminated with  the  rod-shaped  bacteria  as  well  as  with  the  spotted 
fever  organism. Later  researchers,  however,  confirmed  Ricketts's 
finding  of  nonpathogenic  rickettsiae  in  many  noninfective  ticks. 

Between  19 16,  when  Wolbach  wrote  his  first  preliminary  report, 
and  19 1 9,  when  he  pubHshed  the  comprehensive  study,  he  apparently 
resolved  his  questions  about  the  different  coloration  Ricketts  had  ob- 
served and  described.  Control  of  acidity  in  laboratory  studies  was  not 
well  understood  before  1920,  and,  as  Edmund  V.  Cowdry  at  the  Rock- 
efeller Institute  noted,  by  varying  the  composition  of  Giemsa's  stain, 
either  the  red  or  the  blue  coloration  could  be  enhanced.  "The  frequently 
noted  tendency  to  be  colored  less  intensely  than  ordinary  bacteria  with 
Giemsa's  stain,"  Cowdry  observed,  was  also  difficult  to  estimate  quan- 
titatively and  varied  "within  wide  limits."^"^  Because  of  this,  it  is  im- 
possible to  ascertain  whether  the  organism  described  by  Lunsford  D. 
Pricks— despite  his  repeated  protestations  to  the  contrary— was  iden- 
tical to  Wolbach's.  After  19 17,  when  Pricks  was  assigned  to  malaria 
control  operations  in  Tennessee,  he  made  no  more  effort  to  defend  the 
organism  he  had  identified." 


A  Wholly  New  Type  of  Microorganism 


109 


In  addition  to  the  difficulty  of  identifying  the  spotted  fever  organism 
under  the  microscope,  the  riddle  of  its  relationship  to  typhus  — the 
disease  it  most  closely  resembled— likewise  remained  unsolved.  Al- 
though the  louse-borne  nature  of  typhus  had  already  been  firmly  es- 
tabhshed,  its  microbial  etiology  remained  shrouded  in  mystery.  In 
19 14,  Harry  Plotz  and  his  colleagues  in  the  Department  of  Pathology, 
Mount  Sinai  Hospital,  New  York,  identified  a  Gram-positive  bacillus 
associated  with  the  blood  of  typhus  fever  victims  and  typhus-infected 
lice.  They  argued  that  this  bacillus  might  play  an  important  causative 
role  in  the  disease.  Two  years  later,  a  Brazilian  researcher,  Henrique 
da  Rocha  Lima,  described  red  staining,  "bluntly  elliptical,  olive- 
shaped"  organisms  "somewhat  smaller  than  the  smallest  bacteria," 
which  had  the  ability  to  penetrate  the  digestive  tract  cells  of  lice  and 
there  to  multiply  rapidly.  Like  spotted  fever,  these  presumed  typhus 
organisms  resisted  all  efforts  at  cultivation.  Even  so,  da  Rocha  Lima 
maintained  that  they  were  the  etiological  agents  of  typhus,  and  he 
named  them  Rickettsia  prowazeki  in  honor  of  Ricketts  and  of  the 
Polish  investigator  Stanislaus  von  Prowazek,  both  martyrs  in  typhus 
research. 

Wolbach,  however,  decUned  to  classify  the  spotted  fever  organism 
with  that  of  typhus.  In  arguing  for  two  different  genus  names,  he  noted 
that  Ricketts's  descriptions  of  the  typhus  and  spotted  fever  organisms 
had  been  "markedly  different."-^^  Wolbach's  name,  Dermacentroxenus 
rickettsi,  was  to  stand  as  the  designation  for  the  spotted  fever  organism 
for  more  than  two  decades  as  he  and  other  researchers  investigated  a 
variety  of  so-called  Rickettsia-bodies  and  their  connection  to  what 
came  to  be  called  the  typhus-Hke  diseases.  Between  19 10  and  1930 
reports  began  to  be  published  from  nearly  every  continent  about  dis- 
eases exhibiting  a  high  fever  and  rash,  usually  occurring  after  a  tick, 
mite,  or  insect  bite.  Although  the  geographical  isolation  of  most  of 
these  diseases  precluded  intensive  laboratory  study,  they  added  an- 
ecdotal evidence  that  these  were  indeed  a  distinct  class  of  diseases. 

In  19 10,  Alfred  Conor  of  the  Pasteur  Institute  in  Tunis  reported 
with  a  colleague  on  a  peculiar  eruptive  fever  in  Tunisia.  Clearly  different 
from  known  Mediterranean  fevers,  this  malady  caused  a  rash  that  was 
"difficult  to  classify  in  the  nosological  framework  of  skin  diseases." 
Although  the  lesions,  which  appeared  "first  on  the  abdomen,  then  on 
the  whole  surface  of  the  body,  including  the  face,"  were  not  "spots 
or  stains  or  pimples,"  Conor  believed  that  the  best  description  for 
them  was  "pimply  lesions."  This  designation,  he  admitted,  might  "lack 
precision,"  but  for  want  of  a  more  explicit  term,  it  appeared  most 


no 


Rocky  Mountain  Spotted  Fever 


useful.  Many  patients  ill  with  the  disease  were  observed  to  have  bites, 
but  these  were  attributed  to  "small  mosquitoes,"  and  tick  bites  were 
never  mentioned. 

The  same  year,  an  American  physician,  Nathan  E.  Brill,  described 
an  unknown  disease  he  had  studied  in  221  patients  for  more  than  a 
decade.  In  1898,  Brill  had  reported  on  apparent  typhoid  cases  that 
produced  no  Widal  reaction  and  displayed  symptoms  of  typhus  fever. 
Having  pursued  this  mysterious  fever  for  so  many  years.  Brill  con- 
vincingly demonstrated  that  it  was  a  distinct,  previously  undescribed 
disease.  No  arthropods  of  any  type  were  connected  with  this  illness, 
but  because  of  the  thoroughness  with  which  Brill  presented  his  case, 
"Brill's  disease"  immediately  attracted  the  attention  of  the  research 
community  and  became  a  catch  all  for  unknown,  typhus-like  symp- 
toms. 

European  researchers  at  colonial  stations  in  Africa  also  enriched  the 
literature  by  describing  a  typhus-Hke  disease  in  southern  Africa.  In 
191 1,  Jose  F.  Sant'Anna  reported  in  Parasitology  that  he  had  seen  six 
patients  in  Louren^o  Marques,  in  Portuguese  East  Africa,  who  suffered 
headache,  joint  pains,  lymph  gland  inflammation,  and  a  slight  papular 
eruption  on  the  fourth  or  fifth  day.  These  symptoms  occurred  after 
the  victims  were  exposed  to  the  bites  of  larval  ticks,  which  were  so 
numerous  in  the  grass  of  Louren^o  Marques  "as  to  constitute  a  ver- 
itable scourge."  Identified  primarily  as  Amblyomma  hebraeum  larvae, 
the  ticks  were  especially  prevalent  in  July  and  August.  Because  cases 
occurred  infrequently  and  victims  recovered  spontaneously,  few  hos- 
pitals had  experience  with  the  disease. 

Sant' Anna's  report  stimulated  G.  H.  F.  Nuttall,  the  editor  of  Par- 
asitology^ to  report  his  own  correspondence  about  tick-borne  fevers 
in  southern  Africa.  A  Johannesburg  physician,  G.  E.  Turner,  Nuttall 
stated,  had  identified  similar  cases  resulting  from  the  bite  of  Am- 
blyomma hebraeum  ticks.  Turner  described  at  the  site  of  the  tick  bite 
"a  kind  of  bleb  over  the  bite,"  from  which  some  "watery  material" 
could  be  squeezed  out,  after  which  a  small  sore  formed.  Later,  this 
lesion  would  be  known  as  the  tdche  noire,  or  eschar,  of  the  disease. 
Victims,  Turner  observed,  were  usually  new  arrivals  to  the  area,  for 
local  inhabitants  seemingly  had  immunity.  C.  W.  Howard,  an  ento- 
mologist in  Lourengo  Marques,  also  reported  additional  cases.  Howard 
recounted  his  own  bout  with  the  fever,  which  had  occurred  "some 
years  ago,"  just  after  his  arrival  and  following  a  tick  bite.  He  also 
noted  that  the  well-known  researchers  Edward  Hindle  and  Frederick 
Breinl  had  contracted  a  similar  fever  at  Runcorn  Research  Labora- 
tories, near  Liverpool,  while  they  were  studying  Amblyomma  he- 


A  Wholly  New  Type  of  Microorganism 


III 


braeum  larvae  sent  from  Capetown.  Because  all  of  these  cases  were 
presumably  connected  to  the  bite  of  a  tick,  Nuttall  proposed  that  the 
African  diseases  be  called  tick-bite  fever  in  order  to  distinguish  them 
from  the  more  general  name,  tick  fever,  which,  he  maintained,  was 
closely  identified  with  Rocky  Mountain  spotted  fever  and  with  re- 
lapsing fever.^^ 

J.  G.  McNaught,  a  member  of  the  Royal  Army  Medical  Corps  in 
South  Africa,  held  a  different  position  about  this  unknown  African 
fever.  In  a  paper  delivered  to  the  South  African  Medical  Congress  in 
191 1,  McNaught  sought  to  distinguish  it  from  paratyphoid  fever,  with 
which  it  had  been  confused.  Although  chnical  symptoms  in  cases  seen 
by  McNaught  were  virtually  identical  to  Nuttall's  tick-bite  fever, 
McNaught  had  observed  tick  bites  in  only  a  few  cases  and  had  been 
unable  to  find  any  "blood  parasites"  in  blood  smears.  Having  just  read 
Nathan  Brill's  paper,  moreover,  McNaught  argued  that  the  unknown 
diseases  in  South  Africa  must  be  the  same  disease  because  of  their 
clinical  similarity.^^ 

In  19 1 7,  J.  W.  D.  Megaw  of  the  Indian  Medical  Service  added  a 
new  disease  to  the  growing  list  by  describing  his  own  encounter  with 
a  fever  contracted  after  a  tick  bite  near  Lucknow  in  the  Kumaon  Hills 
of  the  Himalayas.  Quoting  from  the  19 13  unpublished  report  of  a 
colleague  about  a  disease  identified  as  typhus  in  the  same  vicinity, 
Megaw  determined  that  his  illness  was  identical.  He  maintained,  how- 
ever, that  this  disease  was  not  typhus  but  rather  a  disease  similar  to 
Brill's  disease.  He  argued,  in  fact,  that  all  the  typhus-like  diseases  with 
the  exception  of  typhus  itself  should  provisionally  be  classified  as  Brill's 
disease.  The  etiological  agent,  he  speculated,  was  "probably  an  invisible 
virus,"  which  was  likely  to  have  been  "conveyed  from  man  to  man 
or  from  another  animal  to  man  by  a  biting  insect  or  tick."^^ 

In  the  Far  East,  typhus-like  fevers  were  reported  from  the  Federated 
Malay  States,  Australia,  and  Japan. Although  knowledge  about  those 
in  Australia  and  the  Malay  States  was  Hmited  to  clinical  descriptions, 
the  disease  known  for  centuries  in  Asia  and  called  tsutsugamushi  in 
Japan  was  subjected  to  closer  scientific  scrutiny.^^  In  18 10,  Hakuju 
Hashimoto  described  a  tsutsuga,  meaning  "disease,"  along  the  trib- 
utaries of  the  Shinano  River.  A  similar  disease,  thought  to  be  carried 
by  mites,  or  mushi  in  Japanese,  had  been  known  at  least  since  the 
sixteenth  century  in  southern  China.  Laboratory  investigations  of  tsut- 
sugamushi began  in  Japan  in  the  early  1890s  when  it  captured  the 
attention  of  Shiramiro  Kitasato,  who  returned  from  his  work  with 
Robert  Koch  in  Germany  to  found  the  Institute  for  Infectious  Diseases 
in  Tokyo.  Maintaining  that  the  bite  of  a  red  mite  transmitted  the 


112 


Rocky  Mountain  Spotted  Fever 


disease,  Kitasato  believed  that  he  had  seen  a  protozoan  body  in  the 
red  blood  cells  of  patients.  This  theory  gained  support  from  the  dis- 
tinguished Tokyo  physician  Masaki  Ogata,  himself  a  specialist  in  pro- 
tozoa. Many  of  Kitasato's  colleagues  at  the  Institute  for  Infectious 
Diseases,  however,  favored  a  theory  of  bacterial  causation.  A  third 
theory  held  that  tsutsugamushi  was  the  result  of  a  toxin  contained  in 
the  body  of  the  red  mite.  In  1908,  U.S.  Army  surgeons  Percy  M. 
Ashburn  and  Charles  F.  Craig,  who  had  confirmed  Charles  Wardell 
Stiles's  findings  that  a  protozoan  organism  was  not  the  etiological 
agent  of  Rocky  Mountain  spotted  fever,  conducted  a  comparative  study 
of  spotted  fever  and  tsutsugamushi.  Although  they  noted  these  different 
theories,  they  concluded  only  that  tsutsugamushi  and  spotted  fever 
were  distinct  disease  entities. 

Completing  the  group  of  typhus-like  diseases  known  during  the  first 
two  decades  of  the  twentieth  century  was  yet  another,  newly  discovered 
during  World  War  I.  Known  by  various  names,  including  Wolhynian 
fever,  quintan  fever,  Polish  fever,  Meuse  fever,  and  Russian  intermittent 
fever,  the  descriptive  appellation  given  to  the  disease  by  the  British 
armies  in  northern  France  seemed  most  appropriate:  trench  fever.  This 
disease  never  killed,  but  it  caused  much  misery  and  loss  of  manpower 
in  all  the  warring  armies.  Studies  by  several  commissions,  including 
one  sponsored  by  the  American  Red  Cross,  showed  that  trench  fever 
was  a  member  of  the  typhus  family,  clinically  characterized  by  head- 
ache, joint  and  muscle  pains,  a  high  fever,  and  a  rash.  Half  the  cases 
suffered  relapses  after  the  first  bout.^^ 

The  Great  War  of  19 14-18  in  Europe  provided  the  stimulus  for 
further  intensive  research  on  epidemic  typhus  itself.  Although  typhus 
did  not  harass  the  armies  of  western  European  nations,  it  did  ravage 
those  of  Russia,  Serbia,  and  Poland.  After  the  war  ended,  it  settled 
with  vengeance  on  Polish  civilians.  During  the  19 15  Serbian  epidemic, 
it  was  reported  that  every  fifth  man  in  the  army  was  ill,  and  135,000 
died.  The  Soviet  revolution,  which  ended  the  war  in  Russia,  did  not 
bring  relief  from  this  malady.  Between  19 19  and  1922,  more  than  10 
million  cases  of  typhus  were  reported. Known  to  be  a  disease  of  cold 
climates  and  the  winter  months,  typhus  spread  rapidly  via  its  louse 
vector  in  the  fur-lined  clothing  common  in  northeastern  Europe. 

In  1919,  S.  Burt  Wolbach  was  invited  by  Richard  P.  Strong,  medical 
director  of  the  League  of  Red  Cross  Societies,  to  head  a  commission 
to  study  typhus  in  Poland. Since  Ralph  R.  Parker's  19 17  work  on 
the  anatomy  of  the  tick  had  proven  useful,  Wolbach  invited  Parker  to 
accompany  the  group  for  entomological  studies  on  lice.  After  some 
discussion,  the  Montana  State  Board  of  Entomology  approved  Parker's 


A  Wholly  New  Type  of  Microorganism 


113 


participation.  Unfortunately,  after  Parker  had  traveled  to  Massachu- 
setts to  join  the  group,  he  was  stricken  with  a  respiratory  illness  com- 
plicated by  heart  problems  and  was  unable  to  make  the  journey/°  An 
entomologist  from  the  Lister  Institute,  Arthur  W.  Bacot,  replaced 
Parker,  but  shortly  after  arriving  in  Poland,  Bacot  became  ill  with 
trench  fever  and  had  to  return  to  England.  "We  seemed  to  be  doomed 
to  disappointment  with  entomologists,"  Wolbach  wrote  in  frustra- 
tion.^i 

The  work  of  the  commission,  therefore,  focused  primarily  on  "a 
minute  histo-pathological  study"  of  typhus  lesions  in  humans  and  in 
hce.  This  was  necessary,  Wolbach  maintained,  in  order  to  understand 
typhus  as  a  disease,  and  particularly  "for  appraising  relationships 
between  lesions  found  and  presumptive  etiological  agents  which  might 
be  encountered."  Bacteriological  methods,  he  noted,  were  deliberately 
given  second  importance,  "pending  the  development  of  indications 
during  the  research.""^^  In  his  19 19  paper  on  Rocky  Mountain  spotted 
fever,  Wolbach  had  noted  the  arguments  surrounding  da  Rocha  Lima's 
claim  that  Rickettsia  prowazeki  was  the  cause  of  typhus.  The  Brazilian 
had  not  demonstrated  the  organism  in  vascular  lesions  of  typhus  pa- 
tients, and  such  a  demonstration,  Wolbach  believed,  "would  do  much 
to  settle  the  question."  And  indeed,  the  Red  Cross  typhus  commission 
seemed  to  produce  an  irrefutable  confirmation  of  da  Rocha  Lima's 
findings.  "We  conclude,"  Wolbach  wrote  in  the  commission's  report, 
"that  Rickettsia  prowazeki  is  the  cause  of  typhus."  They  had  found 
not  only  "the  virus  of  typhus  and  Rickettsia  prowazeki''  inseparable 
in  infective  lice,  but  also  "bodies  indistinguishable  from  Rickettsia 
prowazeki^  demonstrable  with  great  regularity,  in  the  lesions  of  typhus 
in  man.'"^^ 

Wolbach  also  incorporated  into  the  commission's  report  a  summary 
of  knowledge  about  Rickettsia-bodies.  Although  he  observed  that  "a 
satisfactory  definition  of  rickettsia  is  not  possible  at  present,"  it  was 
possible  to  note  the  properties  that  the  organisms  held  in  common. 
They  all  had  a  bacterium  like  morphology  but  were  smaller  than 
bacteria.  The  difficulty  of  staining  them  with  solutions  used  for  bacteria 
was  "a  striking  feature,"  as  was  "the  failure  to  retain  the  stain  by 
Gram's  method."  There  were  no  motile  forms.  None  of  the  rickettsiae 
pathogenic  for  humans  had  been  successfully  cultured.  All  had  ar- 
thropod hosts,  were  highly  specific  for  that  host,  and,  except  for  typhus, 
were  transmitted  through  the  eggs  of  the  female  arthropod."^"^ 

No  general  acquiescence  to  the  view  that  Rickettsia-bodies  repre- 
sented a  new  form  of  microorganism,  however,  was  forthcoming  from 
the  worldwide  scientific  community.  Julius  Schwalbe,  Berlin  corre- 


114 


Rocky  Mountain  Spotted  Fever 


spondent  for  the  Journal  of  the  American  Medical  Association^  re- 
marked in  June  192 1  that,  despite  numerous  investigations  on  the 
etiology  of  typhus,  there  was  still  no  common  agreement.  Because 
Rickettsia-bodies  had  not  been  cultured  on  artificial  media,  many  re- 
searchers continued  to  reject  them  as  the  etiological  agents  of  the 
typhus-like  diseases  and  to  support  instead  bacterial,  protozoan,  or 
viral  etiologies.  In  1920,  for  instance,  a  Brazihan  researcher  claimed 
that  typhus  was  caused  by  a  protozoan  organism  of  the  Herpetomanas 
genus,  a  group  that  he  regarded  as  "piroplasms  in  a  farther  advanced 
stage  of  evolution.'"^^  The  Piroplasma  genus  to  which  he  referred,  of 
course,  was  the  one  in  which  Wilson  and  Chowning  had  placed  their 
presumed  spotted  fever  organism.  Two  years  later,  another  Brazilian 
claimed  to  have  cultured  a  different  typhus  organism,  which  he  de- 
scribed as  a  bacterium,  on  ascitic  agar,  a  lifeless  medium. H.  M. 
Woodcock,  a  fellow  at  University  College,  London,  preferred  to  dis- 
pense entirely  with  the  concept  of  disease-causing  Rickettsia-bodies. 
He  argued  that  they  were  merely  the  end  process  of  cell  lysis  and  hence 
the  cause  of  the  typhus-like  diseases  was  "an  abnormal  haemetabolic 
enzyme."  In  1921,  Harry  Plotz's  colleagues  in  New  York  compared 
Plotz's  bacillus  with  Rickettsia-bodies  and  determined  only  that  they 
were  different.  They  withheld  judgment  on  the  precise  relationship 
between  typhus  and  either  organism.  Not  even  discussing  Wolbach's 
claim  that  Rickettsia-bodies  were  unique  organisms,  they  focused  only 
on  the  bacterial  or  protozoan  nature  of  the  organisms,  concluding  that 
the  evidence  remained  insufficient  to  classify  them  as  either."^^ 

One  red  herring  that  complicated  the  picture  further  emerged  from 
the  19 1 6  discovery  of  Viennese  physician  Edmund  Weil  and  his  English 
associate  Arthur  Felix  that  a  strain  of  Bacillus  proteus  was  agglutinated 
by  the  sera  of  typhus  patients. Weil  and  Felix  subsequently  identified 
other  strains  of  B.  proteus  and  numbered  them  sequentially  as  X-i, 
X-2,  etcetera.  They  also  introduced  terms  to  designate  the  motility  of 
the  organisms:  O  organisms  were  nonmotile  while  H  organisms  were 
motile.  Their  work  showed  that  the  O  or  nonmotile  B.  proteus  or- 
ganisms agglutinated  more  specifically  than  did  the  H  organisms.  Of 
all  the  strains  they  isolated,  OX- 19  gave  the  best  results. 

What  Weil  and  Felix  had  developed  was  the  first  serological  test  for 
typhus,  which  quickly  became  known  as  the  Weil-Felix  reaction.  In 
1922,  W.  J.  Wilson  confirmed  in  the  Lancet  that  "although  the  nature 
of  the  specific  etiologic  agent  in  typhus  is  still  uncertain,  and  although 
no  simple  laboratory  test  apart  from  animal  experimentation  is  yet 
available  for  its  recognition,"  the  Weil-Felix  test  using  OX- 19  provided 
a  specific  laboratory  diagnostic  tool  for  confirming  cfinical  diagnosis. 


A  Wholly  New  Type  of  Microorganism  115 

In  1921,  moreover,  a  new  strain  of  B.  proteus  was  identified  by  A.  N. 
Kingsbury,  an  Englishman.  It  appeared  to  be  a  modification  of  OX- 
19  with  distinct  antigenic  differences.  Called  the  OX-K  strain  after 
Kingsbury,  it  agglutinated  sera  of  tsutsugamushi  patients  in  low  di- 
lution and  that  of  victims  of  the  typhus-like  disease  of  Malaya  — later 
shown  to  be  an  antigenic  variant  of  tsutsugamushi  — in  high  dilution.^*^ 

Although  subsequent  studies  revealed  that  the  Weil-Felix  reaction 
was  caused  by  a  chance  antigenic  "fit"  between  the  B.  proteus  and 
the  typhus  organism,  a  few  bacteriologists  declared  that  this  bacillus 
was  the  "exciting  organism"  of  typhus.  It  was  soon  demonstrated, 
however,  that  B.  proteus  alone  would  not  induce  typhus.  Other  in- 
vestigators, including  Felix  himself,  argued  that  B.  proteus  and  the 
typhus  virus  were  simply  variants  of  the  same  organism.  Another 
champion  of  this  theory  was  Max  H.  Kuczynski  of  BerHn,  whose 
assistant,  Elisabeth  Brandt,  died  of  a  laboratory-acquired  Rocky 
Mountain  spotted  fever  infection.  Kuczynski  claimed  to  have  cultured 
a  spotted  fever  variant  of  the  B.  proteus  organism,  but  his  experiments 
were  never  repHcated  in  other  laboratories.^^ 

Finally,  a  few  researchers,  including  the  respected  Europeans  Fred- 
erick Breinl  and  Rudolf  Weigl,  maintained  that  filterable  viruses  were 
the  actual  agents  of  the  typhus-like  diseases.  In  this  theory,  Rickettsia- 
bodies  were  considered  either  coincidental  or  a  variant  form  of  the 
viral  agent.  The  agents  of  spotted  fever  and  typhus  had  been  dem- 
onstrated to  be  unfilterable,  but  that  of  trench  fever  had  been  filtered 
by  the  American  Trench  Fever  Commission. "Filterabifity,"  it  should 
be  noted,  was  one  of  two  links  among  a  variety  of  unidentified  sub- 
microscopic  agents  of  disease  and  was  not  an  entirely  precise  term, 
since  experimental  conditions  such  as  the  type  of  filter  and  the  pressures 
exerted  could  vary.  The  other  link  between  these  agents,  of  course, 
was  their  inabihty  to  be  cultured  on  Hfeless  media. 

Several  investigators,  including  S.  Burt  Wolbach  and  Rockefeller 
Institute  researcher  Peter  J.  Olitsky,  attempted  to  convince  their  sci- 
entific associates  that  Rickettsia-bodies,  like  the  filterable  viruses,  were 
obligate  intracellular  parasites— that  is,  they  multipHed  only  within 
living  cells.  Such  pathogens,  they  argued,  would  have  to  be  grown 
using  the  emerging  method  of  tissue  culture,  and  they  experimented 
with  various  tissue  and  media  combinations.  Unfortunately,  the  crude 
tissue  culture  techniques  then  available  did  not  support  luxurious  mul- 
tipHcation  of  rickettsial  organisms.  The  limitations  of  technique  im- 
peded a  clear  demonstration  that  Rickettsia-bodies  required  the  pres- 
ence of  living  cells  to  multiply.^^ 

Although  definitive  proof  eluded  him,  Wolbach  continued  to  argue 


Rocky  Mountain  Spotted  Fever 


that  the  unique  characteristics  of  Rickettsia-bodies  demanded  modi- 
fication of  Koch's  postulates.  Dismayed  that  many  researchers  adhered 
uncritically  to  the  criteria  established  for  bacterial  diseases  no  matter 
what  laboratory  investigations  revealed,  Wolbach  spoke  out  forcefully 
in  a  1925  speech  to  the  Nev^  York  State  Association  of  Pubhc  Health 
Laboratories. 

I  wish  to  emphasize  and  to  insist  on  the  importance  of  methods  which  may 
be  employed  in  the  face  of  failure  to  cultivate  insect-borne  microorganisms  in 
artificial  mediums.  Properly  conducted  experiments  in  which  the  insect  vector 
serves  as  culture  tube,  after  natural  or  artificial  introduction  of  the  "virus," 
have  yielded  evidence  fully  as  reliable  and  in  my  opinion  less  open  to  mis- 
construction than  in  vitro  cultivation.  I  feel  it  to  be  a  duty  to  challenge  skep- 
ticism based  on  rigid  adherence  to  Koch's  postulates  when  dealing  with  insect- 
borne  diseases.  ...  I  do  not  know  what  to  say  to  those  who,  in  the  face  of 
the  evidence  I  have  assembled,  may  still  insist  that  Rickettsia  prowazeki  is  not 
the  cause  of  typhus,  but  simply  invariably  accompanies  the  virus  of  typhus, 
particularly  to  those  who  assume,  like  Breinl  and  Weigl,  that  the  virus  of 
typhus  in  man  may  be  in  ultramicroscopic  form.  The  same  line  of  reasoning 
may  be  applied  to  all  infectious  agents,  whether  or  not  cultivated  in  test  tubes. 

The  controversy  over  the  relationship  of  Rickettsia-bodies  to  disease 
was  finally  settled  only  as  a  consequence  of  developments  in  research 
on  the  filterable  viruses.  Wolbach  himself  had  remarked  as  early  as 
19 1 2  that  "when  our  knowledge  of  filterable  viruses  is  more  complete, 
our  conception  of  living  matter  will  change  considerably,  and  ...  we 
shall  cease  to  attempt  to  classify  the  filterable  viruses  as  animal  or 
plant."^^  His  views  were  supported  by  many  of  the  leaders  of  virus 
research,  notably  Thomas  Rivers  at  the  Rockefeller  Institute  and 
W.  G.  MacCuUum  of  Johns  Hopkins  University  School  of  Medicine. 
At  the  1925  meeting  of  the  American  Association  for  the  Advancement 
of  Science,  for  example,  MacCullum  observed  that  progress  in  viral 
research  had  been  slow  because  "we  still  use  blindly  the  methods  of 
investigation  worked  out  for  bacteriology."  He  suggested  that  "totally 
different  mediums"  might  be  necessary  for  the  cultivation  of  viruses 
in  addition  to  a  conception  of  their  nature  different  from  existing 
views. 

The  concept  of  microbial  pathogens  as  minute  plants  or  animals, 
however,  was  slow  to  change.  In  a  1930  editorial,  the  Journal  of  the 
American  Medical  Association  observed  that  viruses  might  merely  be 
"unusually  small  or  unusually  flaccid  bacteria  or  protozoa,"  a  concept 
that  "would  not  introduce  any  new  factors  into  current  pathologic 
theory."  There  were,  however,  bacteriologists  who  proposed  a  "non- 
microbic  'liquid  life'  "  theory  and  botanists  who  entertained  the  hy- 
pothesis that  viruses  were  "self-propagating  toxins,  enzymes,  or  'mor- 


A  Wholly  New  Type  of  Microorganism 


117 


bidic  bions.'  "  Should  either  theory  be  correct,  the  Journal  noted,  "such 
transmissible  biochemical  perversion  would  necessitate  radical  revi- 
sions of  present  methods  of  research  and  clinical  attack. "^^ 

In  1935  the  need  for  such  a  radical  revision  in  concept  was  proven 
when  Wendell  M.  Stanley,  a  biochemist  at  the  Rockefeller  Institute, 
crystallized  the  tobacco  mosaic  virus.  Stanley,  who  later  won  a  Nobel 
prize  for  his  work,  viewed  the  virus  as  an  "autocatalytic  protein,  which, 
for  the  present,  may  be  assumed  to  require  the  presence  of  living  cells 
for  multiplication."^^  Before  this  revolutionary  discovery,  viral  re- 
search had  focused  primarily  on  study  of  the  infectious  diseases  caused 
by  the  submicroscopic  agents.  Subsequently,  the  techniques  of  the 
relatively  new  discipHne  of  biochemistry  were  employed  in  an  intense 
period  of  study  that  revealed  the  nucleic  acid  and  protein  composition 
of  viruses— findings  that  rekindled  discussion  about  the  definition  of 
life  itself.^^ 

By  the  late  1930s  viruses  were  accepted  as  different  entities  from 
bacteria  or  protozoa,  as  was  their  property  of  multiplying  only  inside 
living  cells.  With  this  change  in  concept,  the  rigid  adherence  to  Koch's 
postulates  decried  by  Wolbach  finally  ceased  to  be  a  major  barrier  to 
proving  etiology  in  viral  and  rickettsial  diseases.  Because  of  their  com- 
mon characteristic  of  intracellular  multipHcation,  moreover,  the  viral 
and  rickettsial  diseases  came  to  be  thought  of  as  one  group.  In  1939 
the  papers  from  a  symposium  at  the  Harvard  School  of  Public  Health 
were  pubUshed  as  the  first  in  a  long  Hne  of  studies  entitled  Virus  and 
Rickettsial  Diseases.^^ 

By  the  time  this  conference  was  held,  the  diseases  caused  by  the 
pathogenic  Rickettsiae  were  termed  rickettsial  diseases  more  often  than 
typhus-like  diseases,  although  the  etiology  of  many  geographically 
isolated  maladies  in  this  group  remained  unclear.  Wide  usage  of  the 
lower-case  r  implied  a  general  acceptance  of  the  concept  that  these 
organisms  were  the  etiological  agents  of  a  separate  class  of  diseases. 
New  laboratory  techniques  introduced  in  1939— which  will  be  dis- 
cussed in  chapter  9— had  also  proved  useful  for  the  immunological 
typing  of  rickettsial  diseases.  With  these  methods  human  rickettsial 
diseases  were  classified  into  three  groups:  the  typhus  group,  the  Rocky 
Mountain  spotted  fever  group,  and  the  tsutsugamushi  group. 

Because  these  organisms  were  so  small  and  so  difficult  to  study, 
their  taxonomic  classification  remained  fluid  for  some  time.  Da  Rocha 
Lima's  designation  Rickettsia  prowazeki  was  honored  as  the  type  spe- 
cies for  the  typhus  organism,  but  in  1927  Emile  Brumpt,  a  French 
parasitologist,  challenged  Wolbach's  genus  designation  of  the  spotted 
fever  organism,  Dermacentroxenus.  Brumpt  contended  that  it  should 


ii8 


Rocky  Mountain  Spotted  Fever 


be  classed  in  the  genus  Rickettsia  with  the  rickettsi  species  designation 
being  preserved.  In  1936,  Henry  Pinkerton  of  the  Department  of  Pa- 
thology at  Harvard  University  School  of  Medicine  observed  that 
Brumpt  had  not  considered  the  intranuclear  location  of  the  spotted 
fever  organism  nor  "the  important  morphological  differences  between 
it  and  Rickettsia  proivazeki.'"  Thus  Pinkerton  supported  the  separate 
genus  proposed  by  his  mentor,  Wolbach.  In  1940,  Cornelius  B.  Philip, 
an  entomologist  who  had  worked  with  Rocky  Mountain  spotted  fever 
investigations  in  Montana  and  who  was,  at  that  time,  on  the  staff  of 
the  Army  Medical  School  in  Washington,  D.C.,  attempted  to  bring 
some  order  into  rickettsial  taxonomy.  In  a  Mayo  Foundation  lecture, 
Philip  proposed  that  Rickettsia  be  adopted  as  the  genus  name  for  all 
the  pathogenic  rickettsiae,  with  Dermacentroxenus  retained  as  a  sub- 
genus designation  for  the  spotted  fever  organism.  By  the  1957  pub- 
lication of  the  seventh  edition  of  Bergey's  Manual  of  Determinative 
Bacteriology,  the  definitive  reference  work  on  bacteriology,  Philip's 
taxonomic  criteria  had  been  accepted,  as  evidenced  in  his  authorship 
of  the  section  on  rickettsiae.  The  editors  of  the  Manual,  moreover, 
had  adopted  an  international  convention  of  doubhng  the  final  /  of 
most  species  names.  In  this  way  the  Rocky  Mountain  spotted  fever 
organism  received  the  name  by  which  it  is  now  called,  Rickettsia 
rickettsii.^^ 

Although  in  1921  such  standardization  had  not  been  achieved,  in- 
ternational research  on  the  typhus-like  diseases  had  provided  inves- 
tigators with  clues  that  would  prove  fruitful  during  the  ensuing  decade. 
Wolbach's  emphasis  on  pathological  study  of  the  tissues  in  rickettsial 
diseases,  for  example,  provided  strong,  if  not  universally  accepted, 
evidence  that  a  new  type  of  microbe  caused  spotted  fever  and  epidemic 
typhus.  In  the  United  States  most  investigators  accepted  Wolbach's 
findings  and  used  his  techniques  to  confirm  cUnical  diagnoses  of  rick- 
ettsial diseases  at  post-mortem.  When  the  U.S.  Public  Health  Service 
returned  to  the  Bitterroot  Valley  in  1922  to  cooperate  with  Montana 
state  authorities  in  seeking  a  medical  solution  to  the  problem  of  Rocky 
Mountain  spotted  fever,  Wolbach's  research  provided  the  theoretical 
basis  on  which  the  renewed  investigations  were  conducted. 


Chapter  Seven 


The  Spencer-Parker 
Vaccine 

We  must  also  keep  in  mind  that  discoveries  are  usually  not  made  by  one 
man  alone,  hut  that  many  hrains  and  many  hands  are  needed  before  a 
discovery  is  made  for  which  one  man  receives  the  credit. 

Henry  E.  Sigerist,  A  History  of  Medicine 


By  the  early  1920s  the  etiological  agent  of  Rocky  Mountain  spotted 
fever  had  been  identified  and  tick  control  efforts  had  been  implemented 
for  ten  years,  yet  the  disease  continued  to  claim  many  victims  and 
affect  living  conditions  in  Montana's  Bitterroot  Valley.  In  1921  case 
incidence  cHmbed  precipitously  to  eleven  cases  and  eleven  deaths— a 
100  percent  mortahty  rate.  In  some  areas  of  the  valley,  land  prices 
had  dropped  from  $125  to  $15  per  acre.  Potential  income  from  tourism 
v^as  likevs^ise  threatened  by  the  presence  of  the  disease  in  the  valley.^ 
Disturbed  by  these  problems  and  unsatisfied  With,  the  results  of  earlier 
control  measures,  local  citizens  clamored  for  additional  federal  assist- 
ance in  attacking  the  problem.  "A  crisis  has  been  reached  in  the  Spotted 
Fever  situation,"  w^rote  the  manager  of  the  Missoula  Chamber  of  Com- 
merce to  W.  F.  Cogsv^ell,  secretary  of  the  Montana  State  Board  of 
Health.  "A  greater  number  of  deaths  from  this  dreaded  disease  has 
occurred  this  year  than  in  the  past,  despite  the  fact  that  the  people 
generally  are  aw^are  of  the  malady  and  take  precautions  against  it.  The 
people  are  aroused  to  a  very  emphatic  desire  that  the  United  States 
Public  Health  Service  take  an  active  hand  in  the  fight  to  overcome  this 
disease."^ 

Exacerbating  the  situation  w^as  the  laboratory-acquired  spotted  fever 
death  of  Arthur  H.  McCray,  Montana's  first  full-time  state  bacteri- 
ologist. McCray  had  assumed  the  post  in  October  19 17  and  had  taken 
up  spotted  fever  research  during  his  spare  time,  hoping  "to  derive  a 
curative  serum  for  the  treatment  of  the  disease."  In  early  June  1919, 
how^ever,  w^hile  working  in  the  laboratory,  he  w^as  infected.  McCray 
died  on  14  June  1919.^ 


119 


I20 


Rocky  Mountain  Spotted  Fever 


As  secretary  of  the  state  board  of  health  and  president  of  the  state 
board  of  entomology,  Cogswell  wired  the  newly  appointed  surgeon 
general,  Hugh  S.  Cumming,  and  appealed  to  the  Montana  delegation 
in  Congress  for  assistance  in  persuading  the  U.S.  Public  Health  Service 
to  reenter  the  work.  The  surgeon  general  sent  Thomas  Parran,  a  rising 
Service  administrator  and  later  surgeon  general  himself,  to  evaluate 
the  situation.  Parran's  visit  was  widely  hailed  in  the  Montana  press 
as  the  beginning  of  renewed  federal  support  for  spotted  fever  research.^ 
Parran  was  unsure  if  future  cooperative  measures  would  be  productive, 
because  of  past  tensions  between  state  and  federal  authorities  over 
jurisdiction  in  tick  control  efforts.  A  meeting  with  local  civic  groups, 
however,  convinced  him  that  the  general  public  in  the  valley  seemed 
"to  be  awakened  to  the  menace  of  this  disease"  and  was  "very  anxious" 
for  the  Service  to  assist  in  its  eradication.^ 

To  emphasize  the  state's  cooperative  intentions,  Cogswell  obtained 
pledges  of  twenty-eight  hundred  dollars  from  Missoula  civic  clubs  to 
defray  initial  expenses  of  the  work,  and  he  secured  an  abandoned 
school  building  near  Hamilton  to  serve  as  a  laboratory.  The  "sub- 
stantial, two  story  brick  school  building"  that  came  to  be  known  as 
the  "schoolhouse  lab"  was  located  on  the  infected  west  side  of  the 
river  about  two  miles  from  Hamilton.^  Its  West  Valley  Road  site  in 
the  river  bottom  area,  however,  was  considered  free  from  infected 
ticks.  A  consolidation  of  schools  in  Hamilton  had  left  it  empty.  Luns- 
ford  D.  Fricks,  who  inspected  the  facihty  at  the  request  of  the  surgeon 
general,  enthusiastically  wrote; 

This  new  laboratory  is  a  much  more  elaborate  affair  than  any  field  laboratory 
which  has  been  previously  used  in  conducting  spotted  fever  investigations.  It 
is  excellently  lighted— kept  well  heated  and  has  two  sheds  on  the  same  school 
lot  which  can  be  used  for  storing  automobiles  and  supplies.  Dr.  [Ralph  R.] 
Parker  has  installed  the  necessary  shelving,  animal  cages,  and  other  equipment 
including  laboratory  animals. ...  In  addition  to  Dr.  Parker  there  are  at  present 
five  employees  in  the  laboratory— three  at  $150  each  per  month  and  two,  a 
clerk  and  janitor,  at  $90  each.  These  men  have  been  employed  in  equipping 
the  laboratory,  making  maps,  caring  for  animals  and  the  building,  and  will 
be  ready  to  begin  field  investigations  at  any  time  the  season  permits.^ 

Such  concrete  efforts  by  Montana  authorities  proved  convincing, 
hence  on  4  March  1922,  Cumming  detailed  to  Montana  Roscoe  Roy 
Spencer,  the  young  Passed  Assistant  Surgeon  who  in  191 5  had  assisted 
Fricks  in  spotted  fever  work.  The  thirty-four-year-old  Spencer  was 
born  in  1888  in  West  Point,  Virginia,  the  last  of  five  children  of  Branch 
Worsham  Spencer  and  Emma  Roy  Burke  Spencer.  He  took  his  A.B. 
degree  in  1909  at  Richmond  University,  and  in  19 13  he  received  the 


The  Spencer-Parker  Vaccine 


121 


The  sign  over  the  door  identifies  this  abandoned  schoolhouse  on  the  west 
side  of  the  Bitterroot  River  as  a  U.S.  PubUc  Health  Service  Laboratory. 
Widely  known  in  the  1920s  as  the  "schoolhouse  lab,"  this  was  the  site 
where  Roscoe  R.  Spencer  and  Ralph  R.  Parker  ground  up  ticks  to  make  a 
vaccine  against  spotted  fever.  (Courtesy  of  the  Rocky  Mountain 
Laboratories,  NIAID.) 


M.D.  degree  from  Johns  Hopkins  University  School  of  Medicine.  Be- 
lieving that  he  could  "never  assume  a  radiant  bedside  manner,"  Spencer 
joined  the  U.S.  Public  Health  Service  in  19 14  as  an  assistant  in  the 
Hygienic  Laboratory  and  v^as  commissioned  an  Assistant  Surgeon  later 
that  year  by  President  Woodrov^  Wilson.  During  his  191 5  work  on 
spotted  fever,  Spencer  had  not  been  impressed  by  Fricks's  research. 
After  being  recalled  to  Washington  in  the  fall,  Spencer  assumed  he 
w^ould  have  no  further  involvement  v^ith  the  disease.  For  the  next  seven 
years,  he  completed  the  usual  tour  of  duty  stations,  including  plague 
control  in  Pensacola,  Florida.^ 

Although  Ralph  R.  Parker  had  been  in  charge  of  the  board  of  en- 
tomology's work  since  191 8,  the  Service  insisted  that  Spencer  be  placed 
in  charge  of  spotted  fever  investigations  in  1922,  "simply  because," 
as  Fricks  explained  to  Cogswell,  who  had  complained,  "from  a  Service 
standpoint  Dr.  Spencer  out-ranks  Dr.  Parker.  This  is  a  fixed  rule  in 


122 


Rocky  Mountain  Spotted  Fever 


the  Service,  as  you  perhaps  know,  from  which  it  would  be  impossible 
to  deviate."  Spencer,  of  course,  was  a  physician,  and  Parker,  an  en- 
tomologist. The  arrangement  threatened  to  rekindle  the  old  antagonism 
between  the  two  groups,  because  Parker  saw  no  reason  to  relinquish 
his  position  of  authority.  Cogswell,  however,  "had  a  talk"  with  Parker 
about  the  delicacy  of  the  situation,  soothing  his  injured  ego  with  the 
assurance  that  Spencer  "could  come  in  no  other  capacity."  Parker 
decided  to  accept  the  situation  without  further  protest.  When  Spencer 
arrived,  the  two  men  amicably  agreed  that  all  publications  about  spot- 
ted fever  would  be  joint.^ 

Initially,  Spencer  and  Parker  planned  an  ambitious  program  of  field 
investigations  that  would  be  supplemented  with  laboratory  studies  as 
time  permitted.  Parker  planned  a  broad  study  on  the  relationship  that 
ecological  factors— the  distribution  of  vegetation,  rodents,  and  ticks  — 
might  have  to  human  disease  and  to  one  another.  Believing  that  there 
was  a  natural  cycle  regulating  spotted  fever  in  nature,  Parker  especially 
wanted  to  continue  his  work  on  the  links  among  rabbits,  their  ticks, 
and  spotted  fever. The  field  studies  needed  to  implement  such  a 
program,  however,  were  costly,  time-consuming,  and  of  questionable 
value  to  an  improved  tick  control  program.  Fricks,  who  reviewed  the 
plan  for  the  Service,  believed  that  sufficient  investigational  work  had 
already  been  done  to  assure  practical  control  through  grazing  restric- 
tions and  rodent  destruction.  Spencer,  too,  soon  lost  his  enthusiasm 
for  Parker's  wide-ranging  entomological  studies.  For  the  moment,  how- 
ever. Spencer  let  matters  ride  and  concentrated  on  laboratory  studies, 
hoping  that  a  medical  solution  to  the  spotted  fever  problem  might  be 
found. 

Laboratory  methods  for  identifying  natural  spotted  fever  infection 
in  ticks  had  not  changed  significantly  since  Howard  Taylor  Ricketts 
identified  the  guinea  pig  as  an  experimental  animal.  Groups  of  suspect 
ticks  were  secured  by  a  wire  mesh  collar  on  guinea  pigs  and  allowed 
to  engorge  for  several  days,  after  which  the  animals  were  watched  for 
symptoms  of  the  disease.  In  Spencer's  work  with  plague  in  Pensacola, 
however,  fleas  had  been  ground  up  and  injected  into  the  peritoneal 
cavities  of  guinea  pigs,  a  method  that  shortened  the  waiting  period  by 
several  days.  Spencer  suggested  to  Parker  that  they  try  the  same  method 
with  ticks  to  test  for  spotted  fever  infection.  Initially  they  allowed  ticks 
to  feed  on  infected  animals  for  a  time,  after  which  they  were  ground 
up  and  injected  into  guinea  pigs.  This  experiment  worked  well— five 
of  the  six  pigs  developed  spotted  fever.  Continuing  on  this  course,  they 
separated  1,500  ticks  into  102  lots,  and,  without  allowing  them  to 
feed  first,  ground  them  up  and  inoculated  them  into  guinea  pigs.  Sur- 


The  Spencer-Parker  Vaccine 


123 


The  two  "R.R.s"  who  developed  the  first  vaccine  effective  against  Rocky 
Mountain  spotted  fever:  Roscoe  R.  Spencer,  a  physician  in  the  U.S.  Pubhc 
Health  Service  (left)  and  Ralph  R.  Parker,  a  Montana  entomologist 
appointed  as  a  Special  Expert  to  the  Service.  When  the  vaccine  had  been 
demonstrated  effective.  Spencer  returned  to  other  Service  assignments  in 
Washington,  D.C.  Parker  continued  as  director  of  the  Rocky  Mountain 
Laboratory  until  his  death  in  1949.  (Courtesy  of  the  National  Library  of 
Medicine  and  the  Rocky  Mountain  Laboratories,  NIAID.) 


prisingly,  none  of  the  animals  developed  spotted  fever.  Many  proved 
immune  to  subsequent  direct  inoculations  of  known  lethal  doses. 

These  results  appeared  to  indicate  that  Spencer's  new  method  was 
a  failure.  As  Louis  Pasteur  observed,  however,  chance  favors  the  pre- 
pared mind.  No  conclusion  was  drawn  about  the  results  of  the  ex- 
periments until  Henry  Cowan,  a  field  assistant,  killed  a  mountain  goat 
and  brought  it  into  the  laboratory  because  it  carried  many  engorged 
ticks.  These  ticks,  too,  were  emulsified  and  injected,  and  they  un- 
questionably produced  spotted  fever  in  guinea  pigs.  Spencer  and  Parker 
simultaneously  realized  the  significance  of  their  findings.  The  only 
difference  between  the  ticks  that  produced  immunity  and  those  that 
caused  spotted  fever  was  that  the  latter  had  already  had  a  blood  meal 


124 


Rocky  Mountain  Spotted  Fever 


on  an  animal.  A  jubilant  but  cautious  Spencer  wrote  of  this  insight 
and  its  potential  implications  to  Surgeon  General  Hugh  S.  Gumming. 

One  might  be  justified  in  inferring  from  these  results  that  the  virus  in  the  tick 
.  .  .  requires  fresh  animal  blood  to  stimulate  its  growth  and  multiplication. 
There  is  good  reason  to  believe  that  the  inoculated  ticks  which  conferred 
immunity  would  have  produced  fever  if  fed.  In  other  words  the  virus  needs 
to  be  primed  with  fresh  animal  blood  before  it  can  become  infective.  ...  Up 
to  the  present  time  all  attempts  to  attenuate  the  virus  in  vitro  have  met  with 
failure  but  there  appears  now  a  possibility  of  attenuating  it  in  the  body  of  the 
tick  over  a  long  period  of  time." 

Before  Spencer  suggested  the  short  cut  of  emulsifying  and  injecting 
ticks,  no  change  in  virulence  of  the  spotted  fever  organism  had  been 
suspected.  By  altering  the  method,  Spencer  unintentionally  introduced 
a  new  way  of  viewing  the  process.  The  resulting  insight  also  explained 
two  observations  by  earlier  investigators.  First,  as  Spencer  noted:  "this 
view  fits  in  with  the  fact  that  a  tick  must  be  attached  for  some  hours 
before  it  becomes  infective.  The  very  earliest  time  of  infectivity  as 
determined  by  Ricketts  was  1V4  hours  of  feeding  and  8  to  10  hours 
as  an  average."  Second,  it  illuminated  the  origin  of  cases  of  spotted 
fever  that  had  no  history  of  tick  bite.  Spencer  had  already  demonstrated 
that  the  internal  organs  of  infected  animals  would  communicate  the 
disease  when  rubbed  on  shaved  or  scarified  skin.^"^  Since  engorged  ticks 
contained  highly  virulent  organisms,  a  person  who  had  crushed  such 
a  tick  might  transfer  the  disease  on  the  hands  to  any  abrasion  or  cut 
in  the  skin. 

Once  again,  a  fresh  approach  yielded  results  where  previous  inves- 
tigations had  stalled.  With  his  new  insight.  Spencer  reviewed  the  earlier 
work  of  Ricketts  and  Fricks,  in  which  each  had  produced  immunity 
in  guinea  pigs  by  inoculating  them  with  the  eggs  of  infected  ticks,  and 
found  it  suggested  promising  avenues  for  research.  Enthusiastically  he 
wrote  to  Fricks,  "These  experiments  of  yours  and  Rickett's  [sic]  appear 
to  me  now  highly  significant."  Observing  that  they  had  apparently 
attenuated  the  organism  in  tick  eggs  over  time.  Spencer  predicted,  "If 
I  am  correct  in  this  assumption,  it  appears  to  me  that  in  this  direction 
lies  the  road  to  successful  vaccination  of  people." 

Before  more  conclusive  experiments  could  be  undertaken,  however, 
Spencer's  observation  about  the  potentially  infectious  nature  of  en- 
gorged ticks  on  abraded  skin  was  confirmed  in  a  tragic  manner.  William 
Edwin  Gettinger,  an  undergraduate  student  at  Montana  State  Agri- 
cultural College  in  Bozeman,  had  been  hired  at  his  "earnest  request" 
as  a  student  assistant  for  the  summer.  Born  16  July  1899  in  Melrose, 
Iowa,  Gettinger  had  studied  entomology  with  Robert  A.  Gooley  and 


The  Spencer-Parker  Vaccine 


125 


was  saving  money  to  attend  medical  school.  After  the  serendipitous 
discovery  in  April,  Gettinger  assisted  Spencer  in  dissecting  ticks  and 
making  stain  smears  of  their  organs  in  order  to  test  them  for  the 
presence  of  rickettsiae.  Although  never  bitten  by  a  tick,  Gettinger 
apparently  rubbed  at  a  pimple  on  his  neck  repeatedly  w^hile  working 
in  the  laboratory.  In  late  June  he  fell  ill  with  typical  spotted  fever 
symptoms.  It  was  a  fulminating  case,  and  the  young  man  was  soon 
delirious.  Until  he  died  on  30  June  1922,  a  few  weeks  before  his  twenty- 
third  birthday,  Gettinger  "imagined  himself  in  the  laboratory  and 
talked  of  it  constantly."  Gettinger's  death  brought  to  three  the  number 
of  laboratory-acquired  spotted  fever  cases  in  Montana  and  gave  re- 
newed impetus  to  development  of  a  successful  vaccine. 

At  the  end  of  the  summer.  Spencer  left  the  schoolhouse  laboratory 
in  Parker's  care  and  returned  to  the  Hygienic  Laboratory  in  Wash- 
ington, D.C.,  to  continue  his  experiments.  Methodically  he  explored 
various  properties  of  the  spotted  fever  organism  in  light  of  the  previous 
spring's  discovery.  Spencer  demonstrated  that  spotted  fever  rickettsiae 
would  remain  infective  in  animal  tissues  if  kept  in  100  percent  glycerine 
at  a  temperature  constantly  below  —  10°  C  and  that  rickettsiae  could 
readily  be  demonstrated  in  ticks  after  incubation  or  after  feeding  the 
ticks. 

Confident  that  laboratory  work  would  soon  provide  medical  inter- 
vention for  the  disease.  Spencer  apparently  decided  that  his  doubts 
about  the  cost  and  benefits  of  Parker's  broad-ranging  ecological  studies 
were  well  founded.  He  therefore  recommended  that  the  control  work 
be  abolished  or  cut  back  severely.  Spencer's  memo,  however,  ran  into 
trouble  with  Hygienic  Laboratory  director  George  McCoy  and  Surgeon 
General  Hugh  Gumming,  both  of  whom  rejected  the  recommendation. 
Although  they  gave  no  reason  for  their  decision,  it  is  likely  that  earlier 
battles  between  Service  physicians  and  Montana  entomologists  con- 
vinced them  that  tolerance  was  preferable  to  confrontation.^^ 

At  about  this  same  time,  Hideyo  Noguchi  at  the  Rockefeller  Institute 
again  became  interested  in  the  spotted  fever  problem.  Proceeding  along 
the  older  path  of  research  investigated  by  Ricketts,  Noguchi  announced 
in  November  1922  that  he  had  developed  an  immune  serum  for  treating 
a  person  infected  with  spotted  fever.  Instead  of  using  horses,  as  Ricketts 
had,  Noguchi  produced  his  serum  in  rabbits,  declaring  that  it  was 
superior,  "both  in  potency  and  quantity."  In  guinea  pigs,  Noguchi 
wrote,  I  cc  of  the  serum  suppressed  a  spotted  fever  infection  if  given 
within  twenty-four  hours  of  the  tick  bite.  Noguchi  argued  that  guinea 
pig  and  human  susceptibility  to  the  disease  were  comparable  and 
recommended  an  immediate  injection  of  about  16  cc  for  adults  "in 


Rocky  Mountain  Spotted  Fever 


every  instance  when  the  bite  of  a  tick  gives  reason  to  suspect  a  possible 
infection  with  spotted  fever." 

In  Montana  the  news  of  Noguchi's  serum  was  greeted  with  some 
skepticism.  Remembering  the  abortive  efforts  of  Ricketts  and  his  col- 
leagues in  a  similar  attempt,  Cooley  remarked,  "I  do  not  see  that  there 
is  anything  particularly  new  in  .  .  .  [the  serum]  excepting,  perhaps, 
that  he  has  figured  out  the  minimum  dosage  for  a  guinea  pig  and 
computed  the  dosage  for  man."  Nonetheless,  state  board  of  health 
secretary  W.  F.  Cogswell  wrote  to  Noguchi,  requesting  that  he  make 
his  serum  available  for  prophylactic  purposes  in  Montana.  It  was 
doubtful  that  the  serum  could  function  as  a  vaccine,  Noguchi  replied, 
because,  being  a  foreign  protein,  it  would  be  quickly  eliminated  from 
the  body.  He  suggested  that  instead  it  would  be  useful  to  give  the 
serum  to  anyone  bitten  by  an  infected  tick.^° 

During  the  next  few  months,  Noguchi  went  one  step  farther  and 
developed  a  prophylactic  vaccine  by  adding  infected  guinea  pig  blood 
to  the  immune  rabbit  serum.  This  serovaccine  gave  full  protection  to 
guinea  pigs.  Because  of  the  danger  of  using  live  virus,  Noguchi  studied 
the  immunizing  power  of  a  heated  vaccine.  He  concluded  that  heating 
the  mixture  to  56—60°  C  for  twenty  minutes  did  not  destroy  the  im- 
munizing property,  although  it  did  "markedly"  reduce  it.^^  A  decade 
before,  Ricketts  had  pursued  similar  studies  and  abandoned  them. 

Tick  season  in  1923  offered  the  first  opportunity  for  Noguchi's 
serovaccine  to  be  tested  in  humans.  Since  Noguchi  planned  to  come 
to  Montana  for  the  tests,  the  Montana  State  Board  of  Health  capitalized 
on  his  visit  to  further  its  longstanding  goal  of  educating  the  public 
that  spotted  fever  was  a  regional  problem,  not  Hmited  to  Montana. 
In  March  1923  the  board  issued  a  call  to  the  state  and  local  health 
officers  of  the  Rocky  Mountain  region  to  meet  on  5  and  6  April  in 
Missoula  to  discuss  the  current  status  of  Rocky  Mountain  spotted 
fever  in  their  states.  Noguchi  would,  of  course,  be  present  to  discuss 
his  new  vaccine.  S.  Burt  Wolbach  was  likewise  invited,  as  were  rep- 
resentatives of  the  U.S.  Public  Health  Service. 

Papers  were  presented  on  a  wide  variety  of  subjects  relating  to 
spotted  fever,  but  Noguchi's  presence  and  announcement  of  a  vaccine 
overshadowed  all  other  concerns.  Because  of  Noguchi's  Japanese  or- 
igins and  connection  with  the  prestigious  Rockefeller  Institute,  the 
Montana  press  devoted  nearly  as  much  space  to  descriptions  of  the 
famous  investigator  as  to  information  about  the  conference.  "Intensely 
alive,  intensely.  Orientally  poUte— and,  most  intensely,  devoted  to 
science  and  humanity.  That  is  Doctor  Noguchi,"  exclaimed  one  Mis- 
soula reporter.  Under  the  banner  headline  "Spotted  Fever  Heroes," 


The  Spencer-Parker  Vaccine 


127 


another  article  noted  that  nine  Japanese  residents  of  Missoula  had 
volunteered  to  take  the  first  human  injections  of  their  countryman's 
vaccine.-^ 

Although  the  method  of  preparing  the  vaccine  given  to  the  Japanese 
volunteers  was  not  described,  Noguchi  apparently  was  willing  to  risk 
administering  the  live  virus  mixture  in  order  to  achieve  protection. 
This  certainly  seems  to  have  been  his  plan  when  he  offered  the  vaccine 
to  members  of  the  schoolhouse  laboratory  in  Hamilton.  In  an  oral 
histor}-  memoir,  Spencer  recalled  insisting  that  the  vaccine  be  heated 
to  45°  C  in  order  to  kill  the  rickettsiae.  Noguchi  reportedly  opposed 
this  move,  but  he  eventually  complied  and  vaccinated  five  members 
of  the  laboratory  staff.  Later,  other  Bitterroot  Valley  residents  vol- 
unteered, bringing  to  152  the  total  number  of  people  who  took  No- 
guchi's  serovaccme.  A  number  of  them  became  ill  with  serum  sickness, 
possibly  because  the  vaccine  contained  two  t}-pes  of  foreign  proteins  — 
those  in  the  rabbit  serum  and  those  in  guinea  pig  blood. 

The  real  measure  of  the  vaccine,  of  course,  was  whether  it  would 
prevent  the  disease  or  lessen  its  severity'  if  contracted.  Initially  there 
was  an  indication  that  it  was  efficacious.  In  July  after  he  was  vaccinated 
in  April,  Ralph  R.  Parker  sustained  a  laboratory  accident  in  which  he 
knocked  a  syringe  full  of  infected  blood  off  a  table.  It  stuck  in  his  leg 
as  it  fell.  "I  didn't  think  anything  of  it  for  a  few  seconds,"  he  wrote 
to  Cooley,  "and  then  it  dawned  on  me  what  I  had  done."  Parker 
immediately  treated  the  wound  with  iodine  and  "burned  it  out"  with 
nitric  acid.  "I  am  not  worrying  much.  ...  I  think  the  vaccine  is  all 
right.  ...  I  feel  that  there  is  no  danger,  but  of  course  will  feel  uneasy 
for  a  few  days."^-'  Parker  did  not  become  ill,  but  w^hether  the  vaccine 
or  luck  protected  him  was  unclear. 

A  second  case  produced  a  different  outcome.  It  occurred  in  George 
Michky,  Jr.,  son  of  the  laboratory's  janitor.-^  The  child  had  been 
vaccinated  with  Noguchi's  vaccine,  and  although  he  recovered,  he 
suffered  a  long  illness.  Widely  publicized,  the  case  cast  doubt  on  the 
value  of  the  vaccine.  Noguchi  maintained  that  one  case  proved  very 
little  but  noted  that  he  was  attempting  to  develop  a  safe  way  to  ad- 
minister the  more  potent  unheated  vaccine  to  humans.  Spencer  and 
Parker's  immediate  response  to  the  Michky  case  was  to  make  a  large, 
painted  sign,  visible  to  all  approaching  the  schoolhouse  laboratory, 
warning  them  of  the  danger  and  advising  them  that  they  entered  at 
their  own  risk.-' 

Noguchi  discontinued  his  spotted  fever  research  in  November  1923, 
when  he  departed  New  York  for  Brazil  and  turned  his  attention  to 
yellow  fever.  Upon  his  return  in  1925  he  resumed  the  work,  searching 


128 


Rocky  Mountain  Spotted  Fever 


for  a  way  to  produce  a  safe,  potent,  unheated  serovaccine.  Both  Wol- 
bach  and  Parker  viewed  this  work  as  promising,  but  Noguchi  was 
unable  to  protect  monkeys  with  the  preparation,  a  step  he  beUeved 
essential  before  testing  the  vaccine  on  humans.  Increasingly,  he  became 
preoccupied  with  identifying  the  causative  organism  of  yellow  fever. 
After  asserting  that  a  spirochete  was  the  guilty  organism,  Noguchi 
found  his  work  attacked  by  other  researchers.  In  1928  he  traveled  to 
Africa  with  hopes  of  vindicating  his  research,  but  instead  he  contracted 
yellow  fever  and  died.^^ 

Because  of  the  inconclusive  results  obtained  with  Noguchi's  sero- 
vaccine, Roscoe  R.  Spencer  pressed  on  with  his  own  work  after  re- 
turning to  the  Hygienic  Laboratory.  During  the  fall  and  winter  of 
1923-24,  he  continued  to  seek  a  means  to  attenuate  the  organism  and 
produce  a  vaccine.  By  injecting  guinea  pigs  with  various  dilutions  of 
an  emulsion  made  from  the  engorged  ticks,  he  determined  that  1/5,000 
of  a  tick  would  cause  infection  in  a  guinea  pig.  He  refined  his  previous 
experiments  on  the  virulence  of  the  spotted  fever  organism  in  hiber- 
nating, warmed,  and  engorged  ticks.  He  determined  that  the  organism 
in  tick  tissues  was  unfilterable,  a  point  not  examined  by  Ricketts  and 
Wolbach  before  him.  Curiously,  Spencer  found  that  rickettsiae  could 
not  be  demonstrated  in  some  infective  ticks.  Subsequent  studies  threw 
no  additional  Hght  on  this  problem. 

Even  with  much  new  information.  Spencer  could  identify  no  method 
for  translating  it  into  a  usable  vaccine.  The  key  that  unlocked  the 
puzzle  came  from  a  Czechoslovakian  researcher  working  in  Austria 
on  a  vaccine  for  typhus,  spotted  fever's  closest  rickettsial  relative. 
Worldwide  work  on  the  typhus-like  diseases  was  abstracted  in  several 
journals,  including  the  Journal  of  the  American  Medical  Association, 
and  through  these  summaries  Spencer  kept  abreast  of  each  new  de- 
velopment. In  February  1924  he  spotted  the  Journal's  abstract  of  an 
article  originally  published  by  Frederick  Breinl  in  the  Journal  of  In- 
fectious Diseases.  Instead  of  attempting  to  make  a  typhus  vaccine  using 
the  standard  tactic  of  mixing  typhus  organisms  in  blood  with  immune 
serum,  Breinl  demonstrated  that  rabbits  were  actively  immunized  "by 
injecting  emulsified  louse  intestines,  to  which  phenol  has  been  added." 
Protection  was  achieved,  he  speculated,  because  of  the  immunizing 
properties  of  quantities  of  dead  typhus  organisms  present  before  the 
phenol  was  added. 

Spencer  seized  upon  Breinl's  method,  even  though  he  concluded  that 
Breinl's  explanation  of  how  immunity  was  produced  was  not  applicable 
to  spotted  fever.  As  soon  as  he  returned  to  Montana  in  late  February 
1924,  Spencer  prepared  a  vaccine  from  infected  ticks.  From  his  ex- 


The  Spencer-Parker  Vaccine 


129 


periments  on  changes  in  spotted  fever  virulence  in  fasting  and  engorged 
ticks,  Spencer  knew  he  needed  to  use  fully  engorged  ticks  to  obtain  a 
vaccine  that  w^ould  maximize  protective  value.  Using  a  mortar  and 
pestle,  he  ground  up  the  ticks  in  a  salt  solution  to  which  0.5  percent 
phenol  had  been  added  to  kill  the  rickettsiae.  Each  i  cc  dose  contained 
the  equivalent  of  one  tick,  and  since  he  had  determined  the  minimum 
infectious  dose  to  be  1/5,000  of  a  tick,  each  guinea  pig  received  5,000 
infectious  doses  of  killed  vaccine  in  the  injection.  In  every  guinea  pig 
so  inoculated,  the  vaccine  prevented  illness  w^hen  the  animal  was  in- 
jected with  infectious  spotted  fever  blood  fourteen  days  later.^^ 

By  May,  Spencer  had  sufficient  confidence  in  the  vaccine  to  inoculate 
himself  with  it.  Although  it  caused  no  adverse  reaction,  Parker  and 
the  rest  of  the  staff  remained  wary  of  taking  the  vaccine  until  further 
tests  had  been  conducted. There  was  certainly  reason  for  caution. 
Preparing  a  human  vaccine  from  an  arthropod  vector  had  never  before 
been  attempted.  Breinl  had  protected  animals  from  typhus,  but  his 
louse  intestine  vaccine  had  not  been  used  on  humans.  Rabies  vaccine, 
of  course,  was  made  from  the  dried  spinal  cords  of  infected  rabbits 
and  smallpox  vaccine  from  the  pus  in  cowpox  scabs,  hence  the  concept 
of  utilizing  animal  tissues  was  not  new.  Noguchi's  vaccine,  containing 
two  foreign  proteins,  however,  had  caused  adverse  reactions.  Doubtless 
this  memory  dampened  the  staff's  enthusiasm  for  an  unproven  vaccine 
containing  tick  proteins. 

Testing  of  the  vaccine  was  delayed  during  the  spring  and  summer 
of  1924  because  of  a  newly  identified  illness  among  laboratory  workers. 
Shortly  after  Spencer  arrived  in  Montana,  Parker  queried  him  about 
pecuHar  lesions  observed  in  the  laboratory's  rabbits.  Spencer  believed 
the  lesions  were  caused  by  tularemia,  a  disease  with  symptoms  similar 
to  bubonic  plague.  Tularemia  had  first  been  described  in  191 1  by  the 
Hygienic  Laboratory's  director,  George  W.  McCoy,  as  a  plague-like 
disease  of  rodents,  which  he  had  found  while  doing  research  on  plague 
in  Tulare  County,  California.  He  named  the  disease  after  this  location. 
Another  Hygienic  Laboratory  researcher,  Edward  Francis,  had  become 
an  expert  on  tularemia,  demonstrating  that  humans  could  be  infected 
through  handling  infected  rabbits  or  through  the  bites  of  infected  ticks, 
deer  flies,  and  other  arthropods.  Spencer  thus  wrote  to  Francis  about 
his  suspicions,  and  the  senior  man  confirmed  the  diagnosis.  The  dis- 
covery of  tularemia  in  laboratory  animals  stimulated  the  staff  of  the 
Hamilton  laboratory  to  expand  their  studies  into  a  second  tick-borne 
disease.  More  important  to  the  spotted  fever  work,  however,  was  the 
highly  contagious  nature  of  tularemia.  In  July,  Spencer  and  Sam  Ma- 
clay,  an  assistant  bacteriologist,  came  down  with  the  disease.  Both 


130 


Rocky  Mountain  Spotted  Fever 


recovered,  but  Spencer  was  quite  ill  for  several  w^eeks.  After  Spencer 
returned  east,  Parker  himself  contracted  the  disease  and  w^as  ill  for 
seven  v^eeks.^^ 

During  Parker's  bout  with  tularemia,  George  Henry  Cowan  con- 
tracted spotted  fever.  The  son  of  Bitterroot  Valley  pioneers.  Cowan 
had  the  longest  continuous  record  in  the  state  in  spotted  fever  research. 
He  had  begun  working  for  the  U.S.  Bureau  of  Entomology  in  19 13, 
and  his  exemplary  record  had  earned  him  a  promotion  in  19 17  to 
chief  deputy  in  tick  control  work  under  the  Montana  State  Board  of 
Entomology.  When  the  U.S.  Public  Health  Service  took  over  the  work 
in  19  21,  Cowan  had  been  made  a  field  assistant.  His  duties  included 
making  rough  maps  in  the  field,  trapping  experimental  animals,  and 
collecting  ticks  from  animals  and  special  localities. 

Because  Cowan  had  escaped  spotted  fever  despite  a  decade  of  dan- 
gerous work,  one  Montana  newspaper  speculated  that,  "as  many  other 
natives  have  done,  he  perhaps  came  to  regard  himself  as  immune"  to 
the  disease.  He  apparently  contracted  spotted  fever  in  the  laboratory 
through  handling  infected  material,  for  there  was  no  evidence  of  a  tick 
bite.  As  the  thirty-eight-year-old  man  became  sicker,  his  physician 
administered  some  of  Spencer's  vaccine  in  hope  that  it  might  have  a 
therapeutic  effect.  This  effort  was  in  vain:  Cowan  died  on  29  October 
1924.  Parker  wired  Spencer  about  Cowan's  death  and  in  the  same 
telegram  requested  enough  vaccine  to  inoculate  the  laboratory  staff.^^ 

During  the  winter  of  1924-25,  Spencer  tested  his  vaccine  on  mon- 
keys as  well  as  on  guinea  pigs.  Monkeys  provided  an  animal  model 
so  much  closer  to  humans  that  Hideyo  Noguchi  had  written  to  Spencer, 
"If  you  can  protect  Macacus  rhesus  with  your  vaccine,  I  shall  be 
convinced  that  it  will  protect  man."  Spencer  inoculated  eight  monkeys 
with  his  vaccine,  leaving  five  others  unvaccinated  as  controls.  An  im- 
munity test  two  weeks  later  produced  frank  spotted  fever  in  the  con- 
trols, but  all  of  the  vaccinated  monkeys  remained  healthy.  He  also 
tested  for  evidence  of  human  antibodies  to  the  vaccine  by  injecting 
guinea  pigs  with  combinations  of  serum  from  vaccinated  persons  and 
infective  blood  serum.  These  results  indicated  that  the  vaccine  did 
indeed  produce  antibodies  to  spotted  fever.^^ 

When  Spencer  returned  to  Montana  in  the  spring  of  1925,  enough 
vaccine  was  prepared  to  vaccinate  thirty-four  people  in  the  Bitterroot 
Valley— primarily  laboratory  and  field  staff  and  other  residents  whose 
occupations  exposed  them  to  spotted  fever  infection.  Since  human 
dosage  had  not  been  worked  out  precisely,  the  vaccine  was  adminis- 
tered in  two  to  four  doses  of  i  or  2  cc  at  five-day  intervals.  No  severe 
reactions  were  encountered,  but  most  people  reported  local  redness. 


The  Spencer-Parker  Vaccine 


During  the  effort  to  develop  a 
vaccine  against  spotted  fever, 
three  w^orkers  at  the  schoolhouse 
laboratory  became  martyrs  to  lab- 
orator>'-acquired  infections.  Wil- 
liam Edwin  Gettinger  (top  left),  a 
student  assistant  with  the  U.S. 
Public  Health  Service,  died  in 
1922;  George  Henry  Cowan  (bot- 
tom), a  field  assistant  with  the 
Montana  State  Board  of  Entomol- 
ogy and  the  U.S.  Public  Health 
Service,  in  1924;  and  Albert 
LeRoy  Kerlee  (top  right),  also  a 
student  assistant  to  the  Service,  in 
1928.  (Courtesy  of  the  Rocky 
Mountain  Laboratories,  NIAID.) 


132 


Rocky  Mountain  Spotted  Fever 


swelling,  and  heat  for  two  days  around  the  site  of  the  injection.  A  few 
also  suffered  headaches  and  muscular  pains.  One  recipient  observed 
that  his  "hand  became  swollen  and  the  arm  was  somewhat  uncom- 
fortable for  a  while,"  but  that  he  was  able  to  continue  his  regularly 
scheduled  activities.  "I  imagine  that  it  looked  worse  than  it  felt,"  he 
commented.^^ 

The  first  test  of  the  vaccine's  effectiveness  came  unexpectedly  in 
April,  when  E.  O.  Everson,  a  forty-three-year-old  employee  of  the 
Montana  State  Board  of  Entomology,  contracted  spotted  fever.  He 
had  actively  sought  vaccination  because  he  dipped  tick-infected  cattle 
and  often  picked  engorged  ticks  off  by  hand.  The  course  of  his  illness 
was  mild,  and  although  convalescence  was  prolonged,  he  recovered. 
Spencer  noted  that  it  was  impossible  to  state  without  reservation  "that 
the  vaccine  modified  the  course  and  severity  of  the  infection."  Four 
unvaccinated  victims  of  spotted  fever  that  spring,  however,  died  within 
ten  days,  and  since  the  disease  in  persons  over  forty  was  nearly  always 
fatal,  Everson's  recovery  augured  well.^^ 

The  apparent  success  of  the  vaccine  on  a  small  scale  produced  a 
large  demand  for  it  the  following  year,  even  though  it  remained  an 
experimental  product.  Spencer  underwent  surgery  for  appendicitis  in 
March  1926  and  was  unable  to  return  to  Montana,  but  Parker  and 
his  staff  produced  enough  vaccine  to  inoculate  over  four  hundred 
persons,  ranging  in  age  from  four  to  seventy,  in  the  Bitterroot  Valley 
and  in  Idaho.  In  the  southern  valley  town  of  Darby,  school  was  dis- 
missed in  order  to  allow  people  to  be  vaccinated.  Each  person  received 
2  cc  of  vaccine  in  each  of  two  injections  one  week  apart.  Few  severe 
reactions  to  the  injections  occurred;  none  was  fatal.^^ 

Ralph  R.  Parker  and  L.  B.  Byington,  whom  the  U.S.  Public  Health 
Service  had  detailed  to  Montana  in  Spencer's  place,  were  equally  in- 
terested in  analyzing  the  vaccine's  effectiveness  against  the  mild  Idaho 
form  of  spotted  fever.  A  large  concentration  of  Basque  sheepherders, 
whose  occupation  rendered  them  particularly  vulnerable  to  spotted 
fever,  provided  an  ideal  population  for  a  trial  of  the  vaccine  in  Idaho. 
Since  infection  often  took  place  on  the  range  far  from  medical  assis- 
tance, the  incapacitation  of  a  sheepherder  often  meant  loss  of  many 
sheep  to  the  owners.  Idaho  stock  owners  thus  urged  their  sheepherders 
to  take  the  vaccine.  Because  some  resisted  and,  in  any  case,  there  was 
insufficient  vaccine  to  inoculate  all  of  them,  those  not  vaccinated  served 
as  controls  in  studying  the  new  product's  effectiveness.  None  of  the 
94  sheepherders  vaccinated  in  1926  developed  spotted  fever,  while 
thirteen  cases  occurred  among  180  who  had  not  been  vaccinated.  When 
this  test  was  repeated  in  1927,  one  case  occurred  among  99  vaccinated 


The  Spencer-Parker  Vaccine 


133 


men  as  opposed  to  nine  cases  among  184  controls.'^^ 

Three  cases  of  spotted  fever  at  the  laboratory  further  increased 
confidence  in  the  vaccine's  value.  Two  young  vaccinated  laboratory 
attendants,  Martin  Nolan  and  Frank  P.  Merritt,  suffered  only  mild 
bouts  with  the  disease.  When  the  sixty-two-year-old  janitor,  Alex  Chaf- 
fin,  fell  ill,  the  vaccine's  protective  power  was  demonstrated  most 
impressively.  Parker  observed  that  Chaffin's  recovery  was  a  first  "for 
a  man  of  his  years"  in  the  Bitterroot.  "It  is  believed,"  Parker  continued, 
"that  these  .  .  .  cases  place  the  value  of  the  vaccine  outside  any  realm 
of  doubt."4i 

A  four-year  retrospective  study  of  spotted  fever  in  the  Bitterroot 
later  confirmed  these  empirical  observations  of  the  vaccine's  efficacy. 
Spencer  and  Parker  excluded  the  high-risk  laboratory  workers  and 
examined  the  records  of  1,208  residents  of  a  known  infected  zone  on 
the  west  side  of  the  valley.  Of  these,  496  chose  to  be  vaccinated,  while 
712  refused  and  thereby  served  as  controls  in  the  study.  Over  the  four- 
year  period,  only  three  cases  of  spotted  fever  occurred  in  vaccinated 
persons,  and  none  was  fatal.  In  contrast,  nine  cases  occurred  in  the 
control  group,  seven— or  77.7  percent— of  which  were  fatal. 

For  the  next  fifteen  years,  Parker  continued  to  gather  extensive 
records  from  which  he  published  data  confirming  the  efficacy  of  the 
vaccine.  Overall,  vaccinated  adults  experienced  a  74.24  percent  lower 
fatality  rate  than  did  the  unvaccinated.  In  Idaho,  where  the  disease 
had  never  been  virulent,  the  number  of  cases  decreased  markedly  as 
the  number  of  vaccinated  persons  increased.  Scientific  objectivity  re- 
jected the  obvious  conclusion  that  the  vaccine  fully  protected  people, 
for,  as  Parker  acknowledged,  other  factors  such  as  ecological  shifts 
that  were  not  well  understood  could  be  responsible.  Nonetheless,  the 
partial  correlation  convinced  most  people  of  the  vaccine's  protective 
power  and  increased  demand  throughout  the  west."^^ 

Developing  the  best  method  to  mass  produce  the  vaccine  involved 
a  trial-and-error  process.  Parker  worked  with  his  chief  technician,  Earl 
W.  Malone— who  alone  among  all  employees  involved  with  the  vac- 
cine-making process  escaped  spotted  fever  infection— to  find  a  tech- 
nique that  would  yield  a  consistent  level  of  protection  in  all  lots.  Initially 
they  made  the  vaccine  in  the  fall  before  its  distribution  in  the  spring. 
Eventually,  Parker  and  Malone  learned  not  only  that  the  vaccine  re- 
mained potent  after  a  year's  storage  but  also  that  a  more  potent  vaccine 
resulted  if  ticks  were  stored  in  the  cold  room  for  a  year  before  being 
used.  Preservatives  posed  another  problem.  CarboUc  acid,  or  phenol, 
was  originally  used,  but  it  was  found  insufficient  to  kill  all  contami- 
nating organisms.  Parker  switched  to  formalin  for  a  period,  but  it 


Tubes  containing  ticks  were  stoppered  with  cotton  to  permit  oxygen  to  en- 
ter. Their  open  bottoms  were  buried  in  the  damp  earth.  (Courtesy  of  the 
Rocky  Mountain  Laboratories,  NIAID.) 


A  laboratory  technician  decants  Spencer-Parker  vaccine  into  bottles  for 
shipment,  193 1.  (Courtesy  of  the  Rocky  Mountain  Laboratories,  NIAID.) 


The  Spencer-Parker  Vaccine 


135 


caused  the  vaccine  to  appear  cloudy.  Finally  he  adopted  a  combination 
of  the  two  preservatives.  Although  the  formalin  caused  a  slight  stinging 
for  about  five  minutes  after  a  patient  was  injected,  it  ensured  a  sterile 
product  and  generated  no  other  side  effects. 

The  standard  method  finally  adopted  was  expensive,  time-consum- 
ing, and  dangerous.  It  required  four  to  six  thousand  rabbits  and  twenty 
to  thirt)'  thousand  guinea  pigs  for  feeding  the  ticks  in  all  stages  of  their 
development,  for  maintaining  passage  strains  of  spotted  fever,  and  for 
potency  testing  of  the  vaccine.  Initially,  field  workers  collected  thirty 
to  iorvy  thousand  adult  ticks,  which  were  placed  on  rabbits  to  feed 
and  mate.  After  mating,  the  male  ticks  died.  The  females  were  collected 
and  placed  on  a  wire  cloth  over  moist  sand  on  a  tray  in  an  incubator, 
where  they  produced  some  hundred  million  eggs  and  then  died  them- 
selves. 

Approximately  80  percent  of  the  eggs  hatched  into  larvae  after  a 
five-  to  six-week  incubation  period.  At  this  point,  adult  female  rabbits 
were  infected  with  spotted  fever.  On  the  first  day  the  rabbits  ran  a 
high  fever,  they  were  placed  in  "infesting  bags,"  to  which  the  larvae 
of  four  female  ticks  were  added.  This  number  was  the  maximum  that 
could  feed  without  exsanguinating  the  rabbits.  Left  alone  for  twenty- 
four  hours,  the  larvae  attached  to  the  rabbits  and  the  bags  could  be 
removed.  Rabbits  and  ticks  were  placed  in  wire  cages  and  covered 
with  white  cage  bags  to  prevent  the  ticks  from  escaping.  After  four  or 
five  days,  about  one-fourth  of  the  larvae  succeeded  in  engorging  and 
dropped  from  the  rabbits  to  be  caught  in  the  cage  bags. 

The  next  step  involved  empt\'ing  the  cage  bags  into  a  "tick  picker" 
containing  a  series  of  screens  designed  to  separate  out  waste  food  and 
rabbit  feces  from  the  larval  ticks.  The  recovered  larvae  were  put  back 
into  the  incubator  to  molt  into  nymphs,  a  process  that  took  about  a 
month.  The  feeding  process  was  then  repeated  on  a  new  series  of 
infected  female  rabbits,  although  fewer  nymphs  — about  four  hun- 
dred—were placed  on  each  rabbit.  After  the  engorged  nymphs  were 
separated  by  the  tick  picker,  they  were  washed  and  separated  from 
further  debris  in  a  converted  cream  separator  and  dried  with  a  hair 
drier.  Next  they  were  placed  in  pillboxes,  nvo  hundred  nymphs  to  a 
box,  and  returned  to  a  low^  humidit)-  incubator  at  zz°  C  for  several 
weeks  until  they  molted  into  adults.  About  one  million  of  the  one 
hundred  million  original  eggs  survived  to  adulthood.  They  were  stored 
for  six  months  to  a  year  in  a  refrigeration  room  that  simulated  a  normal 
Montana  mountain  winter  temperature. 

When  ready  to  be  used  for  vaccine  production,  the  ticks  were  taken 
from  storage  and  placed  into  a  "tick  separator,"  an  ingenious  device 


1^6 


Rocky  Mountain  Spotted  Fever 


in  which  hve  ticks  were  separated  from  dead  ticks  and  any  cast  skin 
from  the  last  moh.  The  separator  consisted  of  a  cyHndrical  sheet  metal 
container,  into  which  the  stored  ticks  were  placed,  and  an  attached 
glass  tube.  In  a  lighted  cabinet,  the  ticks  migrated  toward  the  Hght— 
that  is,  into  the  glass  tube— leaving  the  dead  ticks  and  refuse  behind. 
These  ticks  were  warmed  in  the  incubator  and  fed  on  guinea  pigs  for 
three  days  to  reactivate  the  virus.  They  were  then  soaked  for  twenty- 
four  hours  in  a  Merthiolate  solution  to  sterilize  the  surface  of  their 
bodies,  after  which  they  were  divided  into  lots  by  weight.  Covered 
with  a  salt  solution  containing  a  2  percent  mixture  of  phenol  and 
formalin,  each  lot  was  emulsified  in  a  Waring  blender  for  two  minutes. 
To  the  deep  orange  liquid  produced  was  added  additional  phenol- 
formalin-saline  diluent  to  bring  the  volume  to  200  cc.  This  crude 
vaccine  was  stored  for  a  week  at  room  temperature  to  kill  the  rickettsiae 
and  any  contaminating  organisms. 

Finally,  the  vaccine  was  diluted  with  another  600  cc  of  saline  without 
additional  preservatives,  bringing  the  volume  to  nearly  a  quart  and 
reducing  the  concentration  of  the  phenol-formahn  preservatives  to  0.5 
percent.  The  vaccine  thus  produced  contained  one  "tick  equivalent" 
in  each  cc.  After  a  few  additional  weeks  of  storage  in  a  cold  room, 
the  vaccine  was  centrifuged  in  order  to  remove  the  tick  tissue.  Guinea 
pigs  were  inoculated  with  each  lot  of  vaccine  to  test  potency,  and 
sterility  tests  were  performed  by  the  biologies  control  section  of  the 
Hygienic  Laboratory  in  Washington,  D.C.  The  lots  that  passed  these 
tests  were  bottled,  labeled,  and  shipped."^^ 

The  enthusiastic  reception  given  the  tick  vaccine  across  the  north- 
western states  was  welcome,  but  some  of  the  attendant  publicity  was 
not  so  well  received.  Bitterroot  Valley  residents,  acutely  sensitive  to 
spotted  fever's  effect  on  property  values,  were  outraged  in  1927  when 
Paul  de  Kruif  chronicled  the  saga  of  vaccine  development  for  the 
magazine  Country  Gentleman. A  former  bacteriologist  who  had 
abandoned  his  career  at  the  Rockefeller  Institute  to  become  a  popular 
science  writer,  de  Kruif  was  renowned  for  his  hyperbolic  style.  Al- 
though a  generation  of  scientists  was  inspired  by  de  Kruif's  book 
Microbe  Hunters^  residents  of  the  Bitterroot  found  little  to  praise  in 
his  description  of  their  valley  crouching  in  fear  of  spotted  fever.  "When 
the  snow  begins  to  rnelt  on  the  hills  the  terror  of  the  spotted  fever 
begins  to  stalk  in  the  Bitter  Root  Valley,"  de  Kruif  wrote.  "In  that  sad 
territory  the  doors  of  the  empty  ranch  houses  creaked  and  whined  on 
the  hinges,  singing  a  lonesome  song  for  fathers  who  had  died  and 
brothers  and  sisters  and  mothers  who  had  gone  away."  De  Kruif's 
style  riveted  readers  and  sold  magazines,  but  Bitterroot  businessmen 


The  Spencer-Parker  Vaccine 


137 


were  convinced  that  the  article  would  discourage  prospective  home- 
owners and  businesses  from  purchasing  land  in  the  valley."^^ 

Shortly  after  the  article  was  published,  the  Northwest  Tribune  ran 
an  article  under  the  banner  headline  "Bitter  Root  Valley  Is  Up  in  Arms." 
Missoula  and  other  Montana  cities  were  also  reported  to  be  "ablaze 
with  a  wave  of  indignation."  Commercial  clubs  in  Victor,  Stevensville, 
and  Darby  joined  with  the  Hamilton  Chamber  of  Commerce  to  send 
a  prote^ing  telegram  to  the  editors  of  Country  Gentleman.  Another 
article  called  de  Kruif 's  story  an  "absurd  fairy  tale."  Believing  that  de 
Kruif  must  have  obtained  material  for  his  story  from  employees  of  the 
schoolhouse  laboratory,  George  L.  Knight,  secretary  of  the  Hamilton 
Chamber  of  Commerce,  wrote  Montana  Congressman  Scott  Leavitt, 
requesting  that  laboratory  employees  be  restricted  in  what  they  could 
say  to  reporters.  "We  have  no  objection  whatever  to  the  facts  being 
printed,"  Knight  asserted.  "The  statements  that  we  do  object  to  are 
the  ones  which  have  in  the  past  been  dressed  up  by  information  ex- 
aggerated and  over-drawn."  Surgeon  General  Gumming  responded, 
but  his  instructions  were  couched  as  "merely  a  caution"  that  employees 
should  be  careful  what  they  said  to  the  press,  so  information  would 
not  be  abused.^^ 

It  was  not  only  articles  in  the  popular  press  that  elicited  hostility 
from  the  guardians  of  the  valley's  public  image.  In  1926,  W.  F.  Cogs- 
well, secretary  of  the  Montana  State  Board  of  Health,  found  himself 
at  the  center  of  unintended  controversy.  A  man  from  Dillon,  Montana, 
whose  daughter's  geology  class  at  Vassar  College  was  scheduled  to 
make  a  field  trip  to  the  west  side  of  the  Bitterroot,  inquired  of  Cogswell 
whether  the  outing  would  be  safe.  Cogswell  replied  that,  as  state  health 
officer,  he  would  do  all  in  his  power  to  prevent  such  a  field  trip  in  the 
spring.  This  letter  stimulated  an  "indignation"  meeting  of  the  Hamilton 
Chamber  of  Commerce,  whose  secretary  threatened  "dire  and  sundry 
things"  against  Cogswell,  including  trying  to  get  him  fired.  In  the  view 
of  the  Chamber  of  Commerce,  Cogswell  had  gone  out  of  his  way  "to 
give  the  Bitter  Root  Valley  a  black  eye."  When  pressed,  however, 
secretary  Otto  Bolen  admitted  that  he  would  not  want  his  own  daughter 
going  into  the  Bitterroot  mountains  during  active  tick  season,  and  he 
agreed  to  discuss  with  Cogswell  how  future  inquiries  should  be  han- 
dled.^^ 

Although  the  danger  of  living  in  the  Bitterroot  Valley  was  period- 
ically overstated  or  minimized,  the  peril  in  which  the  staff  of  the 
schoolhouse  laboratory  worked  was  never  questioned.  In  August  1926, 
Ralph  R.  Parker  suffered  an  especially  bad  moment.  His  wife  Adah 
found  a  tick  attached  to  herself  that,  when  tested,  produced  spotted 


138 


Rocky  Mountain  Spotted  Fever 


fever  in  laboratory  guinea  pigs.  Fortunately,  Mrs.  Parker  had  been 
vaccinated  in  May,  and  the  tick  was  discovered  before  it  had  become 
well  engorged.  She  showed  preliminary  symptoms  of  spotted  fever  but 
never  came  down  with  a  full  case.  A  relieved  Parker  noted:  "The  facts 
appear  to  be  good  circumstantial  evidence  of  the  value  of  the  vaccine, 
but  it  is  far  from  a  pleasant  thing  to  accumulate  evidence  from  one's 
own  wife.  The  curse  of  this  work  is  not  the  danger  to  one's  self  but 
the  continual  fear  of  bringing  infection  home."^° 

With  the  discovery  of  tularemia  in  the  laboratory's  rabbits,  more- 
over, another  hazard  was  added  to  the  burden  under  which  researchers 
and  their  staff  labored.  In  May  1925,  Earl  W.  Malone,  the  chief  vaccine 
maker,  contracted  tularemia.  His  incapacitation  brought  to  six  the 
number  of  spotted  fever  or  tularemia  infections  among  the  laboratory 
staff  in  just  one  year.  Infected  ticks  from  the  vaccine-making  process 
often  were  found  attached  to  laboratory  personnel,  and  the  school- 
house  design  of  the  laboratory  even  allowed  dogs  to  wander  in  oc- 
casionally. As  the  dangers  compounded,  the  staff  came  to  believe  that 
the  only  way  to  make  the  work  safer  was  to  build  a  new  laboratory.^ ^ 

Beginning  in  early  1925,  the  Montana  State  Board  of  Entomology 
explored  possible  sources  of  funding  for  a  new  facility,  the  total  cost 
of  which  was  estimated  to  be  fifty  thousand  dollars.  Robert  A.  Cooley 
wrote  to  the  Anaconda  Copper  Mining  Company,  the  Rockefeller 
Foundation,  and  the  U.S.  Public  Health  Service,  but  all  hesitated  to 
commit  the  necessary  monies.  Since  spotted  fever  was  known  only  in 
the  northwestern  states,  the  Service  preferred  that  these  states  pool 
their  funds  to  support  vaccine  production.  Although  some  interest  was 
expressed  by  a  former  state  health  officer  in  Wyoming,  none  of  the 
northwestern  state  governments  appropriated  funds  for  the  venture. 

In  early  1926  the  quest  for  a  new  laboratory  took  on  additional 
urgency  when  the  original  owners  of  the  schoolhouse  laboratory  pe- 
titioned to  recover  their  property.  A  stipulation  in  the  deed  provided 
that  the  property  would  revert  to  the  Waddell  family  if  the  building 
ceased  to  be  used  as  a  school.  Since  the  Waddells  had  "mentioned  a 
price  at  which  they  would  sell,"  Cooley  presumed  that  their  aim  was 
"to  get  a  sum  of  money  from  somebody  for  the  property."^^  The  school 
board  opposed  the  petition,  claiming  that  a  population  increase  might 
eventually  require  that  the  building  be  reclaimed  as  a  school.  In  1927 
a  court  hearing  the  case  decided  in  favor  of  the  Waddells. 

The  Montana  State  Board  of  Entomology  seized  upon  this  ruling  to 
press  the  state  legislature  for  a  new  building.  Old  friends  of  the  spotted 
fever  researchers  came  to  their  aid  in  this  effort.  S.  Burt  Wolbach,  who 
stopped  at  the  laboratory  during  a  western  trip,  felt  compelled  to  write 


The  Spencer-Parker  Vaccine 


139 


Hygienic  Laboratory  director  George  W.  McCoy  that  he  considered 
the  schoolhouse  "the  most  dangerous  place"  he  visited.  Describing 
laboratory  conditions  as  disgraceful,  Wolbach  asked  McCoy's  help  in 
moving  federal  or  state  authorities  to  secure  a  new  facility.  W.  F. 
Cogsv^ell,  secretary  of  the  state  board  of  health,  also  appealed  to  the 
surgeon  general  for  documentation  that  w^ould  impress  the  state  leg- 
islature. Surgeon  General  Gumming  complied,  intimating  that  a  new 
laboratory  w^as  necessary  to  "make  continued  studies  by  Service  per- 
sonnel possible. "^'^ 

When  the  state  legislature  convened  in  January  1927,  it  appropriated 
sixty  thousand  dollars  to  build  a  nev^  laboratory  and  twenty-five  thou- 
sand dollars  per  year  for  operating  expenses  during  the  next  biennium. 
Once  the  question  of  funding  had  been  resolved,  another  prickly  issue 
arose:  where  should  the  new  laboratory  be  located?  Spencer  argued 
for  Missoula,  a  larger  town  than  Hamilton  and  home  of  the  University 
of  Montana.  Faculty  members  favored  such  a  move,  and  Spencer  as- 
serted that  the  infected  ticks  posed  no  threat  to  the  campus.  "I  carry 
yearly  thousands  of  infected  ticks  with  me  to  Washington,  and  ship 
hundreds  more  to  New  York  and  abroad."  The  state  board  of  en- 
tomology, however,  preferred  that  the  new  laboratory  be  located  in 
Hamilton.  Because  of  additional  research  planned  by  the  board,  Gooley 
stated,  "we  need  to  be  nearer  to  the  field  than  we  would  be  in  Missoula. 
For  the  vaccine  work  I  think  we  could  have  gotten  along  very  nicely 
as  far  away  as  Missoula  but,  all  things  considered,  the  Board  was  of 
the  opinion  it  would  be  better  at  Hamilton."  The  board's  position 
prevailed  when  the  Hamilton  Chamber  of  Commerce  purchased  and 
donated  to  the  state  a  tract  of  land  on  which  the  laboratory  would  be 
built.^^' 

Many  Bitterroot  Valley  residents  vehemently  opposed  the  location 
just  outside  the  business  district  in  Hamilton,  in  an  area  known  as 
Pine  Grove.  Of  primary  importance  was  that,  for  the  first  time  ever, 
a  spotted  fever  laboratory  was  to  be  built  on  the  uninfected  east  side 
of  the  river.  Since  no  one  knew  why  spotted  fever  was  restricted  to 
the  west  side,  it  is  not  surprising  that  there  was  opposition  to  a  facility 
that  would  be  rearing  miUions  of  infected  ticks  in  a  previously  safe 
area.  For  two  decades,  furthermore,  the  economic  fortunes  of  the 
Bitterroot  Valley  had  fluctuated  with  the  success  or  failure  of  schemes 
to  irrigate  the  dry  benchlands.  In  1920,  after  the  collapse  of  one  of 
these  efforts,  a  bankruptcy  court  had  ordered  residents  to  form  an 
irrigation  district  to  raise  needed  water  revenues.  The  president  and 
Board  of  Commissioners  of  this  new  Bitter  Root  Irrigation  District 
viewed  a  laboratory  in  Hamilton  as  a  threat.  Siting  it  there,  they 


140 


Rocky  Mountain  Spotted  Fever 


protested,  would  "cause  a  general  feeling  that  the  entire  valley  was  so 
infected,  causing  unjust  damage  to  the  East  Side  farming  lands."^^  To 
protect  their  interests,  they  filed  suit  against  the  state  boards  of  health 
and  entomology  and  against  the  state  board  of  examiners. 

Most  of  those  complaining  were  residents  of  Pine  Grove  who  felt 
that  their  own  property  values  were  threatened.  E.  R.  Hammond,  an 
employee  of  the  local  Light  and  Water  Company,  described  as  the 
"principal  agitator,"  was  joined  by  other  prominent  Hamilton  resi- 
dents, including  a  physician,  a  dentist,  a  pharmacist,  a  judge,  and  an 
engineer  for  the  Bitter  Root  Irrigation  Company.  When  the  first  stir- 
rings of  opposition  appeared,  proponents  of  the  new  laboratory  dis- 
missed it  as  "Cigar  Store,  Drug  Store,  Bridge  Club  and  street  corner 
discussion."  Although  the  case  remained  on  the  court's  calendar,  a 
number  of  the  plaintiffs  soon  dropped  out,  realizing  that  they  would 
be  responsible  for  court  costs  if  the  ruling  went  against  them.^^ 

Cooley  welcomed  this  fight.  He  believed  that  erecting  the  laboratory 
in  Hamilton  would  do  much  to  clear  away  superstition  that  had  sur- 
rounded spotted  fever  for  decades.  He  thus  rebuffed  an  alternative 
proposal  from  Victor  officials,  who  hoped  to  entice  the  laboratory  to 
their  city.  Setting  out  his  opinions  in  a  letter  to  Cogswell,  Cooley  stated: 

The  psychological  influence  of  bringing  this  laboratory  into  town  will  be 
considerable.  One  great  difficulty  in  the  past  has  been  that  people  have  looked 
upon  spotted  fever  as  a  mystery  about  which  the  less  said  the  better.  There 
has  been  too  much  unreasonable  fear  of  it.  To  bring  the  laboratory  into  town 
will  help,  gradually,  to  allay  unreasonable  fear,  and  will  help  to  educate 
everyone.  Some  day  residents  in  that  vicinity  will  say  to  visitors  who  come  to 
the  valley  that  "We  used  to  be  afraid  to  go  across  the  river.  Now  we  have  the 
laboratory  right  in  town."  This  will  do  much  to  reassure  people  who  think 
of  settling  and  making  business  investments.^^ 

On  27  July  1927  the  case  was  heard  by  Judge  George  B.  Winston 
of  the  Fourth  Montana  Judicial  District.  The  plaintiffs'  testimony  fo- 
cused on  the  dangers  already  documented  at  the  schoolhouse  labo- 
ratory. Field  assistants  were  described  as  coming  back  with  ticks  "on 
their  horses  and  clothing,  and  their  beds,  and  they  will  ride  up  to  the 
institution."  Since  field  workers  were  seeking  "the  most  malignant  and 
wild  — the  most  virulent  and  dangerous  ticks,"  there  was  fear  that  they 
would  carry  them  home  if  the  laboratory  was  in  Hamilton.  It  was 
noted  that  ticks  had  escaped  in  the  yard  of  the  laboratory  and  alleged 
that  the  janitor  had  been  "the  sole  protector  of  the  community."  Coun- 
tering suggestions  that  children  playing  near  the  proposed  site  would 
be  at  risk,  Cogswell  testified  that  there  would  be  no  chance  for  the 
experimentally  infected  ticks  to  escape  from  the  laboratory.  The  vivid 


The  Spencer-Parker  Vaccine 


141 


Built  by  the  state  of  Montana  in  1928  for  spotted  fever  vaccine  production, 
this  laboratory  was  located  in  Hamilton,  Montana,  on  the  uninfected  east 
side  of  the  Bitterroot  River.  To  prevent  infected  ticks  from  escaping,  it 
incorporated  many  special  features,  such  as  rounded  seams  where  walls  met 
floors  and  a  moat  around  its  perimeter,  across  which  ticks  reportedly  could 
not  swim.  (Courtesy  of  the  Rocky  Mountain  Laboratories,  NIAID.) 

testimony  caught  the  attention  of  the  Journal  of  the  American  Medical 
Association,  which  reported  that  "the  question  of  how  fast  these  ticks 
travel  is  said  to  have  enlivened  the  court  proceedings."  Judge  Winston 
ultimately  sided  with  the  researchers  and  ruled  that  construction  of 
the  laboratory,  begun  in  mid  June,  should  continue. 

With  the  court  case  behind  them,  the  sponsors  of  the  new  laboratory 
concentrated  on  tick  proofing  the  facility,  which  was  occupied  in  May 
1928.  The  laboratory  was  built  of  reinforced  concrete,  brick  faced. 
Around  the  perimeter  of  the  building  was  a  moat  containing  water, 
across  which  ticks  supposedly  could  not  swim.  Outside  it  was  a  "tick 
yard,"  used,  in  part,  for  storing  hibernating  ticks.  An  animal  house 
was  attached  to  the  main  building,  and  the  whole  complex  was  sur- 
rounded by  a  fence  to  keep  out  "rodents,  domestic  animals,  and  boys." 
In  addition  to  several  laboratory  rooms,  refrigeration  rooms,  and  gen- 
eral offices,  there  were  specially  designed  tick-rearing  and  vaccine- 
producing  rooms.  The  joints  between  floor  and  walls  were  all  rounded 
to  prevent  ticks  from  hiding.  A  chamber  through  which  workers  passed 
on  entering  or  leaving  the  tick-rearing  room  contained  mirrors  for 


142. 


Rocky  Mountain  Spotted  Fever 


examining  their  bodies.  Eventually  a  device  v^as  also  installed  to  heat 
their  stored  clothing  to  150°  F  for  six  minutes  in  order  to  kill  any  ticks 
hiding  in  the  fabric  seams. 

These  extraordinary  precautions,  soHcitous  public  relations,  and 
evidence  that  no  children  playing  near  the  laboratory  became  infected 
soothed  the  tensions  raised  by  construction  of  the  facility.  Within  a 
few  years,  in  fact,  the  problem  reversed  itself:  townspeople  visited  the 
laboratory  so  often  as  to  make  themselves  a  nuisance.  It  had  become, 
Cooley  noted,  "a  rather  popular  place  for  visitors  to  go.  People  in 
town  like  to  take  their  guests  out  there  and  show  them  through  the 
building."  Fearing  that  an  accidental  infection  might  take  place,  Parker 
ordered  all  employees  to  get  permission  before  taking  visitors  through 
the  building.^^ 

Parker  had  some  cause  for  concern,  because  even  with  the  best  advice 
on  constructing  the  building,  unanticipated  dangers  were  eventually 
discovered.  Infected  ticks  were  found  hiding  around  the  windows  and 
screens,  in  a  pile  of  sacks  that  had  lain  undisturbed  for  some  time  in 
the  corner  of  a  room,  and  in  the  nickel  caps  around  pipes  going  through 
the  floor.  Ticks  also  escaped  via  the  cage  sacks  used  in  the  tick-rearing 
process.  After  each  use,  these  sacks  were  sent  down  a  chute  into  a 
creosote  solution  that  was  supposed  to  kill  any  remaining  ticks  before 
the  sacks  were  washed.  The  solution  was  discovered  to  be  ineffective 
when  ticks  were  found  in  the  laboratory's  backyard  where  the  sacks 
were  dried.  Subsequently  the  bags  were  soaked  in  kerosene  and  boiled 
in  soap  before  washing.^^ 

Ironically,  none  of  these  precautions  would  have  prevented  a  lab- 
oratory-acquired spotted  fever  infection  that  occurred  at  the  school- 
house  laboratory  just  three  months  before  the  new  facility  was  com- 
pleted. No  infected  tick  was  found  attached  to  LeRoy  Kerlee,  a 
Bitterroot  Valley  native  and  student  volunteer  at  the  laboratory,  who 
became  ill  on  4  February  1928.  W.  F.  Cogswell  speculated  that  Kerlee 
might  have  contracted  the  disease  through  a  skin  abrasion  or  by  rub- 
bing his  eye  with  a  contaminated  finger.  Because  Kerlee  had  received 
injections  of  the  Spencer-Parker  vaccine,  his  illness  provoked  suspicions 
among  some  local  doctors  that  the  vaccine  itself  had  caused  the  disease. 
Roscoe  R.  Spencer  and  Ralph  R.  Parker  launched  an  immediate  in- 
vestigation of  the  case,  which  revealed  that  the  young  man  had  not 
received  the  full  vaccine  regimen.  On  i  and  6  September  1927,  Kerlee 
had  received  i  and  2  cc,  respectively,  of  vaccine— whereas  two  injec- 
tions of  2  cc  each  were  the  norm.  Spencer's  research  had  shown  that 
the  vaccine's  protective  power  lasted  only  a  few  months,  so  Kerlee's 
immunity  had  probably  not  been  carried  over  into  1928.  On  30  January 


The  Spencer-Parker  Vaccine 


143 


1928,  Kerlee  had  taken  i  cc  of  vaccine,  only  one-fourth  of  the  complete 
series.  Records  on  the  lot  of  vaccine  shovv^ed  that  it  had  protected  all 
six  guinea  pigs  on  which  it  was  tested.  Parker  speculated  that  Kerlee 
had  been  infected  either  before  receiving  the  1928  injection  or  almost 
immediately  thereafter. 

There  was  some  indication  that  these  minimal  doses  of  vaccine 
affected  the  course  of  Kerlee's  illness.  Four  days  after  the  onset  of 
symptoms,  he  seemed  to  rebound.  He  got  out  of  bed  and  shaved  but 
soon  felt  exhausted.  This  short  period  of  remission,  Parker  beheved, 
indicated  that  the  virus  and  the  antibodies  produced  by  the  vaccine 
were  "fighting"  and  that  the  vaccine  almost  won  on  that  morning. 
When  Kerlee's  temperature  shot  up  to  104°  F  that  same  afternoon,  he 
was  taken  to  the  hospital.  His  condition  deteriorated  rapidly,  and  a 
week  later,  on  15  February,  he  died.  In  death  the  promising  young 
scientist  was  honored  almost  like  a  military  hero.  His  brother,  refusing 
to  be  intimidated  by  the  deadly  disease,  applied  before  the  funeral  for 
a  position  at  the  laboratory. 

Kerlee's  death  unsettled  Bitterroot  citizens  and  threatened  the  vac- 
cine program  at  the  laboratory.  In  an  effort  to  allay  fears,  Cogswell 
published  a  newspaper  article  trying  to  explain  to  Bitterroot  Valley 
residents  that  this  singular  case  did  not  invalidate  the  effectiveness  of 
the  Spencer-Parker  vaccine.  He  noted  that  occasionally  vaccines  failed 
in  individuals  even  though  they  were  effective  on  a  broad  scale.  Fur- 
thermore, he  argued,  the  spotted  fever  strains  maintained  at  the  lab- 
oratory were  the  "most  virulent  form  of  the  poison,  much  more  virulent 
than  that  found  in  nature."  At  the  laboratory  itself,  a  morose  Spencer 
wrote  Surgeon  General  Gumming  that  the  situation  had  "caused  a 
gloom  to  be  cast  over  our  personnel."  Not  only  had  they  lost  a  friend, 
Spencer  noted,  but  fear  generated  by  the  death  had  prompted  Lawrence 
McNeal,  who  was  in  charge  of  the  infected-tick-rearing  room,  to  resign 
effective  20  February.  "This  position  in  the  tick  room  is  the  most 
dangerous  in  our  laboratory,"  Spencer  observed,  and  informed  the 
surgeon  general  that  it  was  impossible  to  replace  McNeal  with  another 
immune  individuals^' 

Spencer's  depression  hastened  his  decision  to  leave  Montana.  In 
contrast  to  his  U.S.  Public  Health  Service  colleague  Lunsford  D.  Fricks, 
Spencer  had  never  come  to  love  hving  in  the  Bitterroot  Valley.  Both 
he  and  his  wife  preferred  the  sophistication  of  Washington,  D.G.,  to 
the  isolation  of  Hamilton,  and  neither  enjoyed  the  Bitterroot's  cool 
climate.  Uneasy  with  the  dangers  of  spotted  fever  research,  Mrs.  Spen- 
cer was  "very  anxious"  that  her  husband  finish  his  work  and  move 
on  into  something  new.  Spencer  himself  admitted  that  the  intellectual 


144 


Rocky  Mountain  Spotted  Fever 


challenge  of  the  work  lay  in  vaccine  development— the  mechanics  of 
vaccine  production  did  not  interest  him.  He  therefore  asked  for  and 
was  granted  orders  relieving  him  of  duty  in  Montana  at  the  end  of 
the  summer  of  1928.^^ 

Over  the  next  two  years,  as  credit  for  their  achievement  began  to 
be  accorded  to  Spencer  and  Parker,  the  old  physician-entomologist 
rivalry  surfaced  momentarily.  In  August  1928,  Parker  presented  a  paper 
on  the  spotted  fever  work  to  the  Section  on  Medical  and  Veterinary 
Entomology  of  the  Fourth  International  Entomological  Congress  at 
Ithaca,  New  York.  Spencer  learned  from  a  friend  that  Parker  never 
mentioned  Spencer's  name.^^  This  news  arrived  while  Spencer  was 
preparing  an  exhibit  for  the  American  Medical  Association.  Reacting 
in  an  admittedly  vindictive  manner,  he  left  Parker's  name  off  the  ex- 
hibit, which  was  awarded  the  1930  Billings  Medal  by  the  association.^^ 
Except  for  this  unfortunate  display  by  both  men,  the  two  regarded 
each  other  highly.  After  Spencer  left  Montana,  he  held  a  variety  of 
positions  within  the  U.S.  Public  Health  Service.  From  1943  to  1947 
he  served  as  the  second  director  of  the  National  Cancer  Institute.  After 
retiring  from  the  Service  in  1952,  Spencer  lived  thirty  more  years  in 
retirement.  He  died  10  January  1982  in  Virginia.  He  published  several 
popular  articles  on  spotted  fever,  hoping  to  educate  the  public  about 
the  disease  and  about  the  methods  of  medical  research. 

With  Spencer's  departure  from  Montana  in  1928,  Parker  was  des- 
ignated a  special  expert  by  the  Service  and  placed  in  charge  of  the  new 
laboratory,  despite  some  concern  that  his  lack  of  an  M.D.  degree  would 
strain  the  laboratory's  relations  with  physicians.  Fricks,  who  made 
yearly  inspection  tours  in  the  northwest  states  for  the  Service,  thought 
the  state  health  officers  would  find  it  "more  agreeable"  if  "a  medical 
officer  were  again  placed  in  charge  of  these  activities,"  but  Service 
administrators  supported  Parker's  appointment.  The  surgeon  general 
commented  that  "Dr.  Parker's  excellent  work  should  break  down  any 
opposition  to  him  on  the  part  of  doctors  in  the  Northwest."  Indeed, 
although  Parker  did  not  acquire  another  professional  staff  member 
until  October  1930,  he  managed  to  supervise  vaccine  production  while 
continuing  his  studies  on  the  natural  history  of  spotted  fever.  Parker's 
appetite  for  work,  his  maintenance  of  detailed  records,  and  his  careful 
attention  to  correspondence  won  him  the  respect  and  admiration  of 
Service  officers  and  state  health  officials  alike. 

A  thornier  problem  concerned  long-term  funding  for  vaccine  pro- 
duction. The  Montana  state  legislature  constructed  the  laboratory 
building,  and  the  State  Board  of  Entomology  conducted  field  inves- 
tigations on  entomological  problems,  but  neither  wanted  to  support 


The  Spencer-Parker  Vaccine 


145 


In  193 1  people  lined  up  outside  this  school  in  Darby,  Montana,  to  be 
vaccinated  against  spotted  fever  at  a  free  clinic  sponsored  by  the  U.S.  Public 
Health  Service.  R.  R.  Hayward,  M.D.,  a  local  physician,  administered  the 
vaccine.  (Courtesy  of  the  Rocky  Mountain  Laboratories,  MAID.) 


the  costly  vaccine  program.  The  U.S.  Public  Health  Service  had  agreed 
to  fund  vaccine  development,  assuming  that  a  successful  product  v^ould 
be  produced  commercially  or  by  state  health  departments.  Producing 
a  vaccine  from  ground-up  ticks,  however,  limited  the  location  of  any 
production  facility  and  imposed  costs  and  dangers  that  made  it  an 
intimidating  venture.  George  W.  McCoy,  director  of  the  Hygienic 
Laboratory,  summed  up  the  dilemma  when  he  toured  the  northwest 
states  in  April  1928  to  assess  the  impact  of  the  Spencer-Parker  vaccine. 

The  question  as  to  the  means  of  supplying  the  vaccine  ultimately,  if  the  early 
promising  results  of  its  use  are  fulfilled,  is  a  difficult  one.  No  commercial  firm 
is  likely  to  be  interested  in  its  manufacture  and  sale.  It  seems  to  be  an  un- 
profitable field  for  the  Service  once  the  research  features  are  disposed  of  and 
for  each  state  to  manufacture  its  own  supply  would  be  most  wasteful  by  reason 
of  the  necessity  for  the  duplication  of  plant  and  personnel.  Perhaps  a  pooling 
of  the  interests  of  the  several  states  concerned  would  be  the  logical  procedure."^ 

Although  the  future  of  vaccine  production  remained  uncertain,  most 
people  in  the  Bitterroot  Valley  and  in  other  western  areas  welcomed 


Rocky  Mountain  Spotted  Fever 


the  vaccine,  accepting  its  theoretical  underpinnings  about  microor- 
ganisms, antibodies,  and  tick  transmission  without  the  skepticism  that 
had  characterized  their  forebears.  Parker's  statistics  and  their  own 
experience  vaHdated  the  vaccine's  effectiveness.  Scientifically  the  Spen- 
cer-Parker vaccine  was  a  tour  de  force,  the  first  human  vaccine  prepared 
from  the  bodies  of  arthropod  vectors  and  the  first  effective  medical 
intervention  against  spotted  fever.  Spencer  and  Parker  owed  much  to 
the  earlier  investigators  who  had  struggled  with  Rocky  Mountain 
spotted  fever  for  more  than  two  decades  as  well  as  to  international 
research  on  typhus  and  its  related  maladies.  Their  own  ingenuity  and 
persistence,  however,  especially  in  culturing  rickettsiae  in  their  tick 
hosts  and  in  devising  the  complex  process  for  making  the  vaccine,  had 
produced  the  long-sought  preventive,  and  for  that  achievement  they 
won  the  respect  and  gratitude  of  people  throughout  the  Rocky  Moun- 
tain states. 


Chapter  Eight 


Spotted  Fever 
outside  the  Rockies 

Disease  is  very  old  and  nothing  about  it  has  changed.  It  is  we  who  change 
as  we  learn  to  recognize  what  was  formerly  imperceptible. 

John  Martin  Charcot,  De  I'expectation  en  medecine 


In  1926,  a  young  girl  in  Terre  Haute,  Indiana,  was  playing  in  a  pile 
of  gravel  when  she  discovered  a  "brown  and  black  bug  the  size  of  a 
'butter  bean'  "  attached  to  her  scalp  behind  her  right  ear.  Although 
she  had  not  been  out  of  the  immediate  vicinity,  she  later  developed  a 
high  fever  and  headache,  which  were  accompanied  by  a  rash  and  a 
"pronounced  sleepy  condition"  from  which  it  was  difficult  to  rouse 
her  even  for  food,  Uquids,  and  medication.  Her  physician  diagnosed 
Rocky  Mountain  spotted  fever.  ^  Similar  isolated  cases  of  spotted  fever 
outside  the  Rocky  Mountain  region  had  been  reported,  but  their  num- 
bers seemed  too  small  to  be  significant. 

East  of  the  Mississippi  River,  physicians  usually  diagnosed  cases 
displaying  the  symptom  complex  of  high  fever,  headache,  stupor,  and 
a  rash  as  typhus  fever  or  Brill's  disease.  These  two  diseases  had  been 
viewed  as  identical  since  19 12,  when  John  F.  Anderson  and  Joseph 
Goldberger  demonstrated  that  Brill's  disease  and  epidemic  typhus  fever 
produced  cross-immunity  in  guinea  pigs.  Brill's  disease,  with  its  milder 
clinical  course  and  lower  mortality,  often  became  the  default  diagnosis 
when  physicians  encountered  typhus-like  symptoms  with  no  reports 
of  Hce  or  of  contagiousness.^  In  1926,  however,  U.S.  Public  Health 
Service  investigator  Kenneth  F.  Maxcy  demonstrated  in  a  brilliant 
epidemiological  study  that  an  "endemic"  form  of  typhus  existed  in 
the  southeastern  states.  Although  clinically  indistinguishable  from  ep- 
idemic typhus,  endemic  typhus  produced  a  lower  mortality  rate,  con- 
sistently under  5  percent.  Classic,  epidemic  typhus  was  clearly  con- 
tagious, while  endemic  typhus  occurred  sporadically.  No  lice  were 
associated  with  endemic  typhus  cases,  but  some  sort  of  vector  seemed 
to  play  a  role  in  the  disease.  Maxcy  suggested  that  a  parasite  of  the 


147 


148  Rocky  Mountain  spotted  Fever 

rat  might  be  one  potential  vector.  Since  no  arthropod  vector  had  been 
associated  w^ith  Brill's  disease,  it  appeared  that  endemic  typhus  rep- 
resented a  third  distinct  manifestation  of  typhus.^ 

Maxcy's  work  did  not  explain  the  odd  cases  of  typhus-like  symptoms 
in  the  east  that  varied  from  all  three  patterns.  In  1930,  for  instance, 
a  Virginia  physician,  R.  D.  Glasser,  reported  a  case  of  typhus-like  fever 
following  the  bite  of  an  Amblyomma  americanum  tick.  This  tick, 
though  known  as  an  occasional  parasite  of  man,  had  never  before 
been  implicated  in  the  transmission  of  disease.  Glasser  also  thought 
the  case  noteworthy  because  animals  injected  with  the  victim's  blood 
did  not  show  typical  typhus  signs.  Moreover,  the  Weil-Felix  test  for 
typhus  produced  consistently  negative  results."^ 

Glasser's  report  might  have  remained  yet  another  medical  curiosity 
had  not  the  National  Capital  Area  itself  suffered  an  increase  in  what 
were  presumed  to  be  endemic  typhus  cases  in  1930.  In  late  June  the 
Washington  Post  noted  several  cases  from  Alexandria  and  Fort  Hum- 
phreys, Virginia,  northward  through  rural  Maryland.  Additional  cases 
were  soon  reported,  one  in  the  city  of  Baltimore.  By  mid  July,  when 
nineteen  cases  with  five  deaths  had  been  reported,  federal  and  state 
health  officials  from  Virginia,  Maryland,  Delaware,  and  Pennsylvania 
held  a  conference  in  Baltimore  and  agreed  to  cooperate  in  a  broad 
epidemiological  and  laboratory  study  of  the  typhus  problem.^ 

Representing  the  federal  government  at  this  meeting  was  U.S.  Public 
Fiealth  Service  officer  RoUa  Eugene  Dyer,  who  had  taken  up  Kenneth 
F.  Maxcy's  work  on  typhus  in  1929,  when  Maxcy  resigned  from  the 
Service  to  accept  an  appointment  at  the  University  of  Virginia.  Born 
in  Ohio  and  reared  in  Kentucky,  Dyer  had  studied  medicine  at  the 
University  of  Texas  Medical  Branch.^  He  entered  the  Service  in  19 16 
and  rose  rapidly  through  the  ranks,  rotating  through  the  usual  duty 
stations  until  1921,  when  he  joined  the  Hygienic  Laboratory  staff. 
Within  a  year,  he  had  been  named  assistant  director  of  the  laboratory. 
In  1925  he  published  an  authoritative  paper  on  scarlet  fever  antitoxin, 
and  in  1929  the  laboratory  director,  George  W.  McCoy,  asked  him  to 
set  up  a  typhus  unit,  assigning  two  Service  officers,  Lucius  F.  Badger 
and  Adolph  S.  Rumreich,  to  assist  him. 

Dyer,  Badger,  and  Rumreich  operated  out  of  laboratory  buildings 
at  Twenty-fifth  and  E  Streets,  N.W,  in  Washington,  D.C.  These  red 
brick  buildings  had  housed  the  Hygienic  Laboratory  since  1904,  and, 
after  the  laboratory  was  renamed  the  National  Institute  of  Health 
(NIH)  in  May  1930,  they  remained  the  principal  locus  of  service 
research  until  1938,  when  operations  were  transferred  to  a  much  larger 
campus  in  Bethesda,  Maryland.^  In  their  laboratory  the  NIH  typhus 


spotted  Fever  outside  the  Rockies 


149 


Rolla  E.  Dyer,  who  headed 
the  National  Institute  of 
Heahh  (NIH)  typhus  unit 
and  later  served  as  director 
of  the  NIH,  demonstrated  in 
193 1  that  Rocky  Mountain 
spotted  fever  was  also  pres- 
ent on  the  east  coast  of  the 
United  States.  (Courtesy  of 
the  National  Library  of 
Medicine.) 

team  injected  blood  from  a  Virginia  case  into  guinea  pigs,  hoping  to 
establish  a  strain  of  typhus  in  the  experimental  animal.  Before  con- 
clusive observations  could  be  made,  Dyer  was  called  to  Garfield  Hos- 
pital in  Washington  to  see  a  case  diagnosed  as  typhus  fever.  He  asked 
Roscoe  R.  Spencer  to  go  v^ith  him  and  provide  an  additional  opinion. 
"We  sav^  the  patient  and  decided  that  the  doctor  w^as  right,  that  the 
patient  had  typhus  fever,"  Dyer  recalled  in  an  oral  history  memoir, 
"but  as  we  w^alked  down  the  hill,  Spencer  remarked,  'If  I  had  seen 
that  case  in  Montana,  I  would  have  called  it  spotted  fever.'  "  Spencer's 
uncertainty  triggered  a  new  line  of  thinking  in  Dyer's  mind.  Upon 
returning  to  the  NIH,  he  sent  to  Montana  for  a  strain  of  spotted  fever, 
which  he  established  in  guinea  pigs.  When  he  tested  it  against  those 
strains  isolated  from  rural  Virginia  patients,  he  had  a  clear  answer: 
the  rural  cases  were  not  typhus  at  all.  They  were  Rocky  Mountain 
spotted  fever.  ^ 

Armed  with  this  critical  information.  Dyer,  Badger,  and  Rumreich 
launched  a  full-scale  study  of  the  two  diseases  along  the  eastern  sea- 
board. "Most  of  the  cases  living  in  rural  districts,"  they  reported,  as 
well  as  "urban  dwellers  vacationing  in  the  country,  suffered  from  a 
very  severe  disease,  which  did  not  correspond  to  the  clinical  picture 
of  endemic  typhus,  and  which  resembled  spotted  fever  of  the  Rocky 
Mountains  more  closely  than  it  did  any  other  disease.  A  quite  high 
proportion  of  these  cases  gave  a  history  of  tick  bite  within  a  short 
time  preceding  onset."  They  analyzed  the  geographic  distribution,  gen- 


I50 


Rocky  Mountain  Spotted  Fever 


eral  symptoms,  nervous  and  mental  symptoms,  and  complications  of 
ICQ  selected  cases  that  included  both  Rocky  Mountain  spotted  fever 
and  typhus.  Disturbances  of  the  central  nervous  system  were  more 
severe  in  the  patients  with  spotted  fever.  Convalescence  was  more 
prolonged  and  was  often  accompanied  by  deafness,  visual  disturbances, 
slurred  speech,  and  mental  confusion  that  persisted  for  weeks.  No 
deaths  occurred  among  the  endemic  typhus  cases,  while  among  "93 
cases  of  the  Rocky  Mountain  spotted  fever  type  ...  21  died— a  case 
fatality  rate  of  zz.6  percent."  The  Journal  of  the  American  Medical 
Association  found  this  work  of  great  interest.  It  would  "help  to  clear 
up  another  obscure  type  of  disease,"  the  Journal  opined,  "and  will 
place  the  public  in  the  eastern  part  of  the  United  States  on  guard 
against  being  bitten  by  ticks. "^ 

One  key  question,  however,  remained  unanswered.  How  did  the 
victims  of  typhus  and  Rocky  Mountain  spotted  fever  contract  their 
illnesses?  Almost  half  of  the  spotted  fever  cases  reported  a  definite 
history  of  tick  bite  within  three  weeks  before  the  onset  of  symptoms. 
A  few  victims  remembered  crushing  engorged  ticks  removed  from  dogs. 
All  the  cases,  moreover,  occurred  under  conditions  in  which  tick  bite 
was  possible.  In  contrast,  the  relation  between  victims  of  endemic 
typhus  and  any  arthropod  was  less  clear.  The  epidemiological  evidence 
confirmed  Maxcy's  suggestion  that  rodents  were  somehow  involved: 
78  percent  of  the  typhus  cases  had  occurred  in  close  association  with 
rats.  Only  16  percent  of  typhus  victims,  however,  reported  actual 
contact  with  rats  and  only  8  percent  recalled  having  received  flea  bites. 
To  answer  these  questions,  the  NIH  typhus  unit  launched  another 
study.  Experimentally,  they  soon  demonstrated  that  spotted  fever  could 
be  preserved  in  the  body  of  the  American  dog  tick,  Dermacentor 
variabilis.  The  key  to  demonstrating  tick  transmission,  however,  was 
locating  infected  ticks  in  nature.  By  1932,  Badger  accompHshed  this, 
collecting  naturally  infected  D.  variabilis  from  a  farm  in  Virginia  on 
which  a  human  case  had  occurred.  ^° 

Even  before  the  spotted  fever  vector  was  confirmed,  the  typhus  unit 
recovered  typhus  rickettsiae  from  fleas  on  rats  caught  at  typhus  foci 
in  Baltimore,  Maryland,  and  in  Savannah,  Georgia.  Dyer  announced 
this  exciting  finding  in  a  paper  presented  at  the  193 1  annual  meeting 
of  the  American  Medical  Association.  The  news  precipitated  animated 
discussion  among  other  rickettsial  researchers  present.  Hans  Zinsser 
of  Harvard  University  Medical  School,  who,  with  his  Mexican  col- 
laborator M.  Ruiz  Castaneda  and  a  Swiss  pathologist,  Herman 
Mooser,  had  recently  demonstrated  that  rats  were  one  reservoir  of 
endemic  typhus  fever  in  Mexico,  was  not  convinced  that  fleas  were 


spotted  Fever  outside  the  Rockies 


The  common  dog  tick,  Dermacentor  variabilis,  is  the  principal  vector  of 
spotted  fever  in  the  eastern  United  States.  (Courtesy  of  the  Rocky 
Mountain  Laboratories,  NIAID.) 

the  sole  vector.  Zinsser  favored  the  bedbug  because  of  his  personal 
experience  in  Vera  Cruz,  Mexico,  a  town  teeming  with  rats  and  fleas 
but  free  from  typhus.  Kenneth  F.  Maxcy  argued  that  epidemiologic 
evidence  clearly  ruled  out  bedbugs,  and  Rolla  E.  Dyer  buttressed  Max- 
cy's  position  by  noting  that  Zinsser  himself  admitted  the  possibiUty 
of  mild  or  subclinical  cases  of  unrecognized  typhus  in  Vera  Cruz.^^ 

This  debate  reflected  the  vigor  of  rickettsial  research  in  the  early 
1930s.  Zinsser  optimistically  predicted  that  both  typhus  and  spotted 
fever  investigations  in  the  United  States  were  reaching  a  "coordinating 
phase"  because  of  "a  gradual  encirclement"  by  epidemiologic  and 
experimental  methods. His  positivism  was  doubtless  influenced  by 
the  expansion  of  knowledge  about  typhus  in  Mexico  to  which  Zinsser 
and  his  associates  had  recently  contributed.  Their  discoveries  had 
helped  to  estabUsh  additional  criteria  by  which  typhus-hke  diseases 
across  the  globe,  including  Rocky  Mountain  spotted  fever,  could  be 
studied. 

The  disease  called  tabardillo,  or  Mexican  typhus  fever,  for  example, 
changed  scientific  identities  during  the  studies  of  Zinsser,  Castaneda, 
and  Mooser.  The  Mexican  people  had  used  the  descriptive  term,  mean- 
ing "red  cloak"  to  describe  fevers  that  exhibited  a  particular  symp- 
tomatic rash,  whether  they  occurred  in  summer  or  winter  and  whether 


152 


Rocky  Mountain  Spotted  Fever 


the  mortality  was  high  or  low.  When  Howard  Taylor  Ricketts,  Joseph 
Goldberger,  and  John  F.  Anderson  studied  "tabardillo"  in  Mexico  City, 
they  saw  an  epidemic,  louse-borne  disease  that  occurred  during  the 
winter  and  spring  months.  By  the  late  1920s,  however,  researchers 
began  to  realize  that  the  endemic  typhus  fever  described  by  Maxcy 
was  also  widespread  in  the  Mexican  highlands.  Also  called  tabardillo, 
this  disease  occurred  primarily  in  the  summer  and  fall  and  exhibited 
a  low  mortality.  During  the  intensive  investigation  of  this  new  disease 
that  followed,  the  name  tabardillo,  as  well  as  the  phrase  Mexican 
typhus  fever,  soon  became  identified  solely  with  endemic  typhus.  Ep- 
idemic typhus  in  Mexico  became  known  as  European  typhus  in  order 
to  distinguish  it.^^ 

In  19 17,  before  this  distinction  had  been  made,  U.S.  Public  Health 
Service  officer  Mather  H.  Neill  had  described  a  scrotal  reaction  in 
guinea  pigs  infected  with  "typhus  fever"  from  the  Mexican  highlands. 
Although  Neill  noted  that  it  was  milder  than  the  reaction  induced  by 
spotted  fever,  it  had  not  been  observed  in  guinea  pigs  inoculated  with 
European  strains  of  typhus  or  with  Brill's  disease.  Neill's  paper  was 
nearly  forgotten  until  1928,  when  Mooser  cited  it  to  support  his  own 
similar  findings.  He  also  described  cells  packed  with  rickettsiae  in  the 
tunica  vaginalis,  the  lining  over  the  testes.  These  cells  came  to  be  called 
Mooser  cells,  and  the  tunic  reaction  in  guinea  pigs,  which  served  as  a 
test  to  distinguish  between  endemic  and  epidemic  typhus,  became 
known  as  the  Neill-Mooser  phenomenon.^'*  This  form  of  typhus  fever 
was  generally  transmitted  by  the  rat  flea,  but  if  introduced  into  a  louse- 
infested  population,  it  could  become  epidemic  like  its  better-known 
relative.  Mooser  thus  pointed  out  that  the  name  endemic  typhus  was 
not  truly  descriptive.  In  1932  he  proposed  the  name  murine  typhus 
to  indicate  that  the  disease  was  a  natural  infection  of  the  rat.^^ 

Although  such  new  information  helped  to  distinguish  epidemic  and 
murine  typhus,  Brill's  disease  remained  a  puzzling  phenomenon.  In 
the  laboratory  it  appeared  to  be  identical  with  epidemic  typhus,  yet 
its  milder  symptoms  resembled  the  murine  disease.  In  1934,  Zinsser 
conducted  an  epidemiological  study  as  rigorous  as  Maxcy's  work  on 
murine  typhus  that  identified  victims  of  Brill's  disease  as  European 
immigrants  who  had  come  from  regions  where  epidemic  typhus  was 
prevalent.  He  concluded  that  Brill's  disease— later  called  Brill-Zinsser 
disease— was  really  a  recrudescence  of  an  earlier  attack  of  epidemic 
typhus.  This  indicated,  Zinsser  argued,  that  typhus  rickettsiae  could 
remain  dormant  in  the  human  body,  making  typhus  a  disease  in  which 
humans,  rather  than  rodents  or  arthropods,  served  as  the  natural 
reservoir.  If  a  patient  with  Brill's  disease  was  fed  on  by  Hce,  the  insects 


spotted  Fever  outside  the  Rockies 


153 


could  become  infected  and  transmit  the  disease  to  others.  By  this  means, 
apparently  spontaneous  epidemics  of  typhus  might  be  started.  Labo- 
ratory studies  in  the  early  1950s  confirmed  Zinsser's  epidemiological 
reasoning. 

Across  the  Atlantic  Ocean,  Sir  William  Hames  declared  at  a  1930 
meeting  of  the  Royal  Society  of  Medicine  in  London  that  "typhus  in 
the  tropics"  was  "coming  to  judgment  like  a  Daniel,"  with  research 
"throwing  much  new  light  upon  dark  corners  of  the  epidemiological 
world."  The  paper  that  eUcited  Hames's  enthusiastic  comment  was 
given  by  William  Fletcher,  a  British  physician  working  in  Kuala  Lum- 
pur, capital  of  the  Federated  Malay  States.  In  a  review  of  the  typhus- 
like diseases,  Fletcher  had  observed  that  they  were  widely  distributed 
across  the  warmer  parts  of  the  globe,  from  New  York  and  Marseilles 
in  the  northern  hemisphere  to  Adelaide  in  the  southern.  They  com- 
prised, Fletcher  argued,  a  list  of  names  rather  than  a  Hst  of  diseases: 
shop  typhus,  scrub  typhus,  tropical  typhus,  sporadic  typhus,  twelve- 
day  fever,  and  many  others.  Plainly,  some  rational  criterion  for  group- 
ing these  maladies  was  needed. 

During  the  1920s,  J.  W.  D.  Megaw  of  the  Indian  Medical  Service 
had  proposed  classification  according  to  arthropod  vectors:  (i)  louse 
typhus;  (2)  tick  typhus;  (3)  mite  typhus;  (4)  typhus-like  fevers  trans- 
mitted by  unknown  vectors. Fletcher  advocated  a  simpler  scheme 
based  on  geographic  location.  "The  typhus-like  fevers  fall  into  two 
distinct  groups:  a  rural  group  and  an  urban  group."  Rural  types  in- 
cluded Indian  tick  typhus;  tropical  scrub  typhus  of  Malaya,  Mossman 
fever  of  Australia,  Rhodesian  fever,  and  possibly  fievre  exanthematique 
of  Marseilles.  The  urban  group  was  comprised  of  endemic  typhus, 
shop  typhus  of  Malaya,  Sumatra,  and  Java,  and  typhus  endemique 
benin  of  Toulon. 

Fletcher  made  a  strong  case  for  separating  epidemic  typhus  itself 
from  all  the  others.  In  contrast  to  the  well-known  contagiousness  of 
classic  typhus,  he  argued,  the  other  diseases  were  all  noncontagious. 
"A  case  of  typhus  is  a  matter  of  public  concern,"  he  noted,  pointing 
out  that  no  public  health  authority  in  any  country  quarantined  cases 
of  Brill's  disease  or  murine  typhus.  Other  investigators,  especially 
Charles  Nicolle,  who  had  originally  identified  the  louse  vector  of  ep- 
idemic typhus,  believed  that  the  classic  disease  belonged  to  the  same 
family  as  murine  typhus.  Nicolle  proposed  a  "unity"  theory  of  typhus, 
arguing  that  the  endemic  form  of  the  disease,  because  of  its  association 
with  rodents,  must  be  an  older  form.  Epidemic  typhus  he  regarded  as 
an  "evolved"  form  of  the  endemic  organism. 

The  lack  of  agreement  about  the  classification  and  nature  of  these 


154 


Rocky  Mountain  Spotted  Fever 


diseases  underscored  both  the  vigor  of  the  field  and  the  Umitations  of 
existing  laboratory  technique.  Inability  to  grow  concentrated  quantities 
of  rickettsial  organisms  in  anything  other  than  their  arthropod  vectors 
inhibited  more  direct  study  of  the  immunological  relationships  among 
the  rickettsiae.  The  tiny  size  of  rickettsial  organisms  obscured  the 
details  of  their  morphology.  Rickettsial  disease  research,  in  which  work 
on  Rocky  Mountain  spotted  fever  was  grounded,  thus  continued  to 
be  oriented  toward  the  various  typhus-like  diseases,  rather  than  toward 
the  causative  organisms  themselves. 

Most  interesting  to  Rocky  Mountain  spotted  fever  investigators  were 
foreign  reports  of  new  tick-borne  rickettsial  diseases.  During  1927  and 
1928  in  Marseilles,  France,  an  unusual  typhus-Uke  fever  was  reported. 
Unlike  typhus,  the  rash  of  this  fever  extended  to  victims'  faces,  and  a 
persistent  "black  spot"  was  identified  as  a  possible  point  of  infection. 
In  1930,  French  parasitologist  Emile  Brumpt,  professor  at  the  Faculte 
de  Medicine  in  Paris,  diagnosed  the  Marseilles  epidemic  as  north  Af- 
rican fievre  boutonneuse— the  disease  Alfred  Conor  had  described  in 
19 10  in  Tunis.  In  his  laboratory,  Brumpt  transmitted  this  "Marseilles 
exanthematic  fever"  to  man  through  adult  ticks  reared  from  nymphs 
obtained  on  dogs  in  Marseilles.  Since  ships  traveled  regularly  between 
Marseilles  and  north  African  ports,  Brumpt  suggested  that  the  disease 
had  been  transported  across  the  Mediterranean  in  the  bodies  of  stow- 
away ticks,  and  he  proposed  that  the  causative  rickettsia  be  named 
R.  conori  after  Conor.^^ 

Confirmation  of  fievre  boutonneuse  as  a  new  tick-borne  rickettsiosis 
stimulated  comparative  research  with  Rocky  Mountain  spotted  fever 
on  both  sides  of  the  Atlantic.  In  July  1932,  Brumpt  visited  the  Spotted 
Fever  Laboratory  in  Hamilton,  Montana,  and  collected  infected  ticks, 
which  he  took  back  to  Paris.  He  received  one  injection  of  the  Spencer- 
Parker  vaccine,  but  he  had  such  a  severe  reaction  that  he  did  not  take 
the  prescribed  second  dose.  In  February  1933,  after  returning  to  France 
and  initiating  his  research,  Brumpt  fell  ill.  It  was  finally  determined 
that  he  suffered  from  Rocky  Mountain  spotted  fever,  but  diagnosis 
was  difficult  because  he  was  in  delirium  and  no  previous  case  of  spotted 
fever  had  been  observed  in  France.  Brumpt  was  transferred  to  the 
Hopital  Pasteur  and  eventually  recovered. 

At  the  university  in  Paris,  Brumpt's  illness  produced  a  "considerable 
stir."  Although  he  was  probably  infected  through  a  wound  in  his  hand 
during  a  necropsy  on  an  infected  guinea  pig,  rumors  circulated  that  a 
"vial  containing  the  ticks  had  been  carelessly  broken  by  a  laboratory 
assistant,  that  the  ticks  had  been  scattered  over  the  laboratory,  and 
that  Professor  Brumpt  had  been  bitten."  Students  refused  to  return  to 


spotted  Fever  outside  the  Rockies 


155 


the  building  until  all  tick  vials  were  destroyed  and  infected  guinea  pigs 
were  killed.  The  press  announced  to  the  public  that  Rocky  Mountain 
spotted  fever  could  not  spread  in  France  "by  reason  of  the  climatic 
conditions,"  and  although  this  argument  may  have  had  little  value,  it 
calmed  the  public  mind.  As  soon  as  he  recovered,  Brumpt  requested 
sufficient  spotted  fever  vaccine  to  inoculate  ten  members  of  his  lab- 
oratory staff.^^ 

On  the  western  side  of  the  Atlantic,  NIH  investigator  Lucius  F. 
Badger  also  studied  the  immunological  relationship  between  Rocky 
Mountain  spotted  fever  and  fievre  boutonneuse,  which  Americans 
came  to  call  boutonneuse  fever.  Badger  concluded  that  the  diseases 
were  immunologically  identical,  but  shortly  afterward,  Gordon  E.  Da- 
vis and  Ralph  R.  Parker  at  the  Spotted  Fever  Laboratory  in  Montana 
reported  that  spotted  fever  vaccine  did  not  protect  against  boutonneuse 
fever.  They  speculated  that  the  European  disease  was  less  closely  related 
to  spotted  fever  than  was  another  new  tick-borne  disease  in  Brazil. 

Identified  in  1929  as  Sao  Paulo  "typhus,"  this  disease  struck  sixty- 
eight  people  between  October  1929  and  December  193 1.  Like  the 
Bitterroot  Valley  strain  of  Rocky  Mountain  spotted  fever,  it  exacted 
a  high  mortahty:  80  percent  of  the  victims  died.  Ecologically,  Sao 
Paulo  in  the  1920s  was  similar  to  the  Bitterroot  Valley  at  the  turn  of 
the  century.  During  the  1880s,  Brazilian  coffee  planters,  having 
watched  the  decline  of  slavery  in  South  America,  encouraged  the  im- 
portation of  thousands  of  European  immigrants,  principally  from  Italy. 
This  mass  immigration  had  rapidly  changed  Sao  Paulo  from  a  small 
city  to  a  thriving  metropolis  that  strained  its  public  health  resources. 
By  the  1920s  many  previously  rural  areas  were  becoming  suburbs  of 
the  city.  Human  invasion  of  the  habitat  of  several  local  ticks,  most 
notably  Amblyomma  cajennense^  accounted  for  the  apparently  sudden 
appearance  of  the  disease.  In  1933,  Sao  Paulo  typhus  was  identified 
in  the  nearby  Brazilian  state  Minas  Gerais,  which  had  also  experienced 
a  recent  population  spurt.^^ 

Early  research  on  Sao  Paulo  typhus  was  conducted  by  Jose  Lemos 
Monteiro  of  Sao  Paulo's  Butantan  Institute,  a  facility  famous  for  re- 
search on  snake  venoms.^^  Lemos  Monteiro  showed  the  close  rela- 
tionship between  Rocky  Mountain  spotted  fever  rickettsiae  and  the 
rickettsial  organism  that  caused  the  affliction  in  Sao  Paulo.  He  asserted 
that  Sao  Paulo  typhus  was  "a  native  disease"  with  its  own  individuality, 
and  he  proposed  calling  its  causative  organism  Rickettsia  brasiliensia. 
Emmanuel  Dias  and  Amilcar  Vianna  Martins  at  the  Oswald  Cruz 
Institute  in  Rio  de  Janeiro  and  at  the  Ezequiel  Dias  Institute  in  Bello 
Horizonte  supported  Lemos  Monteiro,  proposing  that  the  disease  be 


156 


Rocky  Mountain  Spotted  Fever 


called  febre  maculosa  hrasileira  in  Portuguese,  or  Brazilian  spotted 
fever  in  English. 

In  1933,  however,  a  series  of  papers  in  Public  Health  Reports  refuted 
the  concept  of  a  new^  disease.  Parker  and  Davis  at  the  Spotted  Fever 
Laboratory  found  that  convalescent  serum  from  patients  v^ith  Sao 
Paulo  typhus  was  protective  against  Rocky  Mountain  spotted  fever, 
which  indicated  a  close  relationship  between  the  organisms.  A  week 
later,  Rolla  E.  Dyer  stated  that  the  two  diseases  were  identical.  Over 
the  next  few  months,  Parker  and  Davis  published  two  additional  papers 
concluding  that  the  "essential  identity  of  these  typhus-like  diseases 
appears  to  be  well  established."^^ 

More  importantly,  these  studies  directly  affected  residents  of  the 
stricken  Brazilian  towns,  for  they  indicated  that  the  Spencer-Parker 
vaccine  should  offer  protection  against  Sao  Paulo  typhus.  And,  indeed, 
once  the  identity  of  the  diseases  had  been  confirmed,  BraziHan  scientists 
persuaded  their  government  to  attempt  large-scale  production  of  the 
vaccine  at  the  Butantan  Institute.  Jose  Lemos  Monteiro  and  his  assis- 
tant, Edison  de  Andrade  Dias,  traveled  to  Montana  in  the  fall  of  1933 
to  study  production  methods  and  to  appeal  for  a  supply  of  vaccine 
until  Brazil  could  produce  its  own.  Although  supplies  were  short  in 
Montana,  1.5  liters  of  the  vaccine  were  sent  to  Sao  Paulo. 

While  visiting  the  Spotted  Fever  Laboratory,  Lemos  Monteiro  and 
de  Andrade  Dias  had  been  routinely  inoculated  with  spotted  fever 
vaccine,  Lemos  Monteiro  taking  two  doses  and  de  Andrade  Dias  a 
single  dose.  In  November  1935,  however,  when  they  began  grinding 
ticks  in  Sao  Paulo  to  manufacture  the  vaccine,  both  became  infected 
with  spotted  fever.  The  Spencer-Parker  vaccine  they  had  received  a 
year  and  a  half  earlier  may  have  lengthened  the  incubation  period  of 
the  disease,  which  was  observed  to  have  been  long.  Tragically,  it  did 
not  save  them:  Lemos  Monteiro  died  seven  days  after  becoming  ill, 
and  de  Andrade  Dias  survived  for  only  five  days.  At  the  Spotted  Fever 
Laboratory,  Ralph  R.  Parker  recorded  these  fatalities,  noting  that, 
ironically,  the  lot  of  vaccine  on  which  they  had  been  working  displayed 
a  high  immunizing  value.  After  this  tragedy,  Emmanuel  Dias  and 
Amilcar  Vianna  Martins  took  over  the  Brazilian  vaccine  program.  Tick 
eradication  methods  for  Sao  Paulo  were  also  investigated,  but  they 
proved  disappointing,  hence  vaccination  was  adopted  as  the  primary 
prophylactic  measure. ^° 

In  1937  another  virulent  epidemic  was  reported  from  Tobia,  Co- 
lombia, a  narrow,  rural,  river  valley  community  located  near  Bogota 
in  the  eastern  range  of  the  Andean  highlands.  Symptoms  of  victims 
and  guinea  pig  reactions  to  inoculations  with  blood  all  pointed  toward 


spotted  Fever  outside  the  Rockies 


157 


an  infection  of  the  Rocky  Mountain  spotted  fever  type,  and  rickettsiae 
were  identified  in  guinea  pig  tissues.  Furthermore,  the  arthropod  vec- 
tors of  all  the  major  typhus-like  diseases,  including  the  tick  that  trans- 
mitted Sao  Paulo  typhus,  were  present  in  the  valley.  From  July  1934 
to  August  1936,  sixty-five  people  had  contracted  the  disease,  and  only 
three  had  survived  — a  mortahty  rate  of  95  percent. 

By  the  early  1940s,  Tobia  petechial  fever,  as  it  was  called,  had  been 
unmasked  as  another  focus  of  Rocky  Mountain  spotted  fever  in  the 
western  hemisphere.  Luis  Patino-Camargo,  director  of  Instituto  Fed- 
erico  Lleras  in  Bogota,  treated  patients,  amassed  epidemiological  data, 
and  compared  strains  of  the  infectious  agent  against  rickettsial  strains 
in  ticks  obtained  from  Parker  in  Montana.  In  the  course  of  this  work, 
one  of  Patino-Camargo's  countrymen.  Hector  Calderon  Cuervo,  be- 
came yet  another  martyr  to  laboratory-acquired  spotted  fever.^^  In 
1941,  Colombian  authorities  requested  a  half-liter  of  the  Spencer- 
Parker  vaccine  for  the  afflicted  area.  One  health  official  wrote  that 
when  the  first  vaccinations  were  performed,  "the  local  civil  authorities 
were  present  and  the  Reverend  Father  Jose  Antonio  Rodriguez,  who 
blessed  the  vaccine  and  gave  a  speech  regarding  the  great  benefits  of 
this  prophylactic  medium  and  the  interest  which  the  National  Gov- 
ernment has  taken  toward  freeing  the  region  of  this  deadly  disease."^^ 

Even  as  Rocky  Mountain  spotted  fever  was  being  unveiled  in  these 
South  American  countries,  certain  aspects  of  the  disease  in  the  United 
States  seemed  to  become  more  baffling.  In  193 1,  when  spotted  fever 
was  identified  in  the  eastern  part  of  the  nation,  the  NIH  typhus  unit 
noted  that  it  killed  about  25  percent  of  infected  guinea  pigs.  In  contrast, 
death  was  "the  rule"  for  those  infected  with  the  Bitterroot  Valley  strain. 
Guinea  pigs  showed  a  scrotal  reaction  with  the  western  strain,  but  it 
had  been  noted  only  once  in  those  inoculated  with  the  eastern  strain. 
"With  these  differences  in  mind,"  Dyer,  Badger,  and  Rumreich  des- 
ignated the  disease  in  the  east  "as  the  eastern  type  of  Rocky  Mountain 
spotted  fever  in  contrast  to  the  western  type  of  the  disease."^"^ 

Almost  at  once,  Ralph  R.  Parker  took  issue  with  the  suggestion  that 
the  disease  occurred  in  two  different  forms.  The  problem,  he  believed, 
lay  in  the  limited  experience  of  most  investigators  with  spotted  fever's 
variations. 

Most  textbook  articles  on  Rocky  Mountain  spotted  fever  and  a  very  consid- 
erable proportion  of  the  papers  by  those  who  have  studied  spotted  fever  in 
and  out  of  the  laboratory  are  too  highly  colored  by  the  fact  that  all  have  done 
most  or  all  of  their  work  with  strains  from  the  Bitter  Root  Valley.  Not  only 
is  this  true,  but  it  is  also  true  that  the  Bitter  Root  Valley  strains  with  which 
they  have  worked  have  been  particularly  selected  for  virulence  and  scrotal- 


158 


Rocky  Mountain  Spotted  Fever 


lesion-producing  power.  As  a  result,  all  of  us,  I  believe,  have  become  too  much 
incHned  to  look  upon  high  fever  and  scrotal  lesions  as  being  part  of  the  typical 
symptomatology  of  Rocky  Mountain  spotted  fever  in  guinea  pigs.  ...  I  have, 
however,  had  extensive  opportunity  to  observe  guinea  pig  reactions  to  strains 
of  lesser  virulence,  not  only  from  other  western  points,  but  also  many  times 
from  the  Bitter  Root  Valley.  ...  I  know,  therefore,  that  there  is  a  marked 
difference  in  guinea  pig  reactions  to  different  strains  and  even  to  the  same 
strain  at  different  times,  and  for  that  reason  the  differences  which  Drs.  Dyer, 
Badger  and  Rumreich  have  noted  do  not  to  me  seem  to  have  the  possible 
differentiating  significance  which  they  apparently  do  to  them.^^ 

Parker  also  cited  documented  differences  in  the  clinical  manifesta- 
tions of  the  disease  in  humans  throughout  the  western  states.  Because 
the  eastern  and  western  strains  produced  full  cross-immunity,  Parker 
argued  that,  barring  other  differences  of  which  he  was  unaware,  they 
were  no  more  different  than  were  those  in  Montana  and  in  Idaho. 
"My  personal  opinion,"  he  concluded,  "is  that  we  will  find  Rocky 
Mountain  spotted  fever  very  widely  distributed  in  nature  in  the  United 
States,  and  that  possibly  human  cases  are  occurring  over  a  much  larger 
territory  than  that  from  which  they  have  thus  far  been  recognized. "^^ 

Although  Parker's  arguments  were  logical  and  grounded  in  personal 
experience,  his  superiors  in  Washington,  D.C.,  believed  that  further 
investigations  were  required,  especially  by  pathologists.  At  the  NIH, 
Ralph  D.  Lillie  took  up  the  question.  The  thirty-five-year-old  LiUie 
had  taken  both  his  undergraduate  training  and  his  M.D.  at  Stanford 
University,  earning  the  latter  in  1920.  At  Stanford  he  was  influenced 
by  William  Ophiils,  a  noted  pathologist  and  student  of  Johannes  Orth, 
who  in  turn  had  studied  under  the  pioneer  cellular  pathologist  Rudolf 
Virchow.  Highly  respected,  Lillie  had  collaborated  with  other  NIH 
researchers  on  problems  ranging  from  pellagra  to  chemical  and  phar- 
macological toxicology  to  infectious  diseases. 

In  193 1,  Lillie  conducted  autopsies  on  four  victims  of  eastern  spotted 
fever  and  studied  histological  material  on  a  fifth.  His  comparisons  to 
the  western  type  of  the  disease  were  made  not  on  direct  observations 
but  on  published  findings  of  the  twenty  autopsies  done  since  1897. 
From  this  limited  number  of  cases,  Lillie  observed  that  certain  differ- 
ences could  be  noted  between  eastern  and  western  spotted  fever.  Bron- 
chopneumonia, he  found,  was  more  frequent  in  the  eastern  type  and 
perhaps  suggested  a  relationship  to  typhus,  in  which  "pneumonias 
have  often  been  seen."  He  also  noted  fatty  changes  in  the  liver,  en- 
largement of  the  spleen,  and  scrotal  gangrene  as  more  frequent  in  the 
western  type.  Focal  brain  lesions,  which  Lillie  found  "constantly  pres- 
ent" in  the  eastern  cases,  were  never  mentioned  in  the  autopsy  reports 
of  western  cases.  These  and  other  differences,  most  notably  the  more 


spotted  Fever  outside  the  Rockies 


159 


prominent  cutaneous  hemorrhages  in  western  spotted  fever,  associated 
with  "its  more  acutely  fatal  course,"  led  him  to  conclude  tentatively 
that  the  diseases  were  indeed  different.^^ 

During  the  next  eight  years,  only  two  pathological  studies  of  eastern 
spotted  fever  cases  were  published,  and  none  appeared  on  western 
cases.  Lillie  himself  studied  the  disease  in  guinea  pigs  and  in  chick 
embryos. As  epidemiological  experience  with  the  disease  in  the  east 
accumulated,  however,  it  became  clear  that  geography  had  little  rel- 
evance to  spotted  fever's  severity.  In  1935,  E.  R.  Maillard  and  E.  L. 
Hazen  of  the  New  York  State  Department  of  Health  noted  a  30  percent 
mortality  rate  among  ten  cases  that  had  occurred  in  upstate  New  York 
between  1926  and  1934.  By  1941  the  NIH  typhus  unit  and  other  U.S. 
Public  Health  Service  investigators  had  isolated  virulent  strains  of  the 
disease  in  ticks  on  the  east  coast  and  strains  of  low  virulence  in  the 
west.  When  mortality  rates  were  compared  over  large  areas  in  each 
region,  moreover,  there  was  virtually  no  difference.'^^ 

Two  1940  clinical  studies  of  larger  groups  of  patients  also  challenged 
the  designations  eastern  and  western  types  of  spotted  fever.  Investi- 
gators working  at  Walter  Reed  General  Hospital  reported  on  seven 
cases  that  occurred  between  193 1  and  1939.  Eugene  R  Campbell  and 
his  collaborator  Walter  H.  Ketchum  concluded  that  they  found  "Httle, 
if  any,  clinical  basis  for  differentiating"  the  two  spotted  fevers.  The 
second  study,  conducted  by  Alfred  L.  Florman  and  Joseph  Hafkenschiel 
of  the  Johns  Hopkins  Hospital,  was  based  on  six  adult  and  fifteen 
pediatric  patients.  They  reported  a  23.8  percent  mortality,  close  to  the 
28.1  percent  mortality  for  the  western  states  compiled  by  the  NIH 
typhus  unit.  Florman  and  Hafkenschiel  also  challenged  Lillie's  dis- 
tinction that  cases  of  eastern  spotted  fever  often  had  bronchopneu- 
monia whereas  the  western  type  did  not.  Only  one  of  their  twenty- 
one  patients  had  bronchopneumonia.  Scrotal  necrosis  was  absent  in 
Lillie's  cases,  but  Florman  and  Hafkenschiel  published  a  picture  of 
this  phenomenon  in  one  of  their  cases.  "It  would  seem,"  they  con- 
cluded, "that  severity  of  infection,  rather  than  geography  or  vector,  is 
of  importance  in  determining  the  pathological  picture. "^^ 

By  1940,  Lillie  himself  had  accumulated  detailed  pathological  in- 
formation on  fourteen  new  cases  of  spotted  fever.  "This  additional 
material,"  he  wrote  in  a  definitive  1941  study  on  the  pathology  of  the 
disease,  "tends  to  amplify  the  picture  of  the  disease  process  and  clarify 
some  of  the  apparent  disagreements  between  the  193 1  report  and  the 
earlier  reports  based  on  cases  occurring  in  the  Rocky  Mountain  area." 
The  differences  noted  in  his  193 1  paper  — bronchopneumonia  and 
brain  lesions  in  the  eastern  cases  and  scrotal  necrosis  and  enlarged 


spotted  Fever  outside  the  Rockies 


161 


spleen  in  the  western  cases— were  more  closely  related  to  the  length 
of  illness  than  to  inherent  differences.  Patients  dying  within  ten  days  — 
a  more  common  occurrence  in  the  Bitterroot  Valley  but  documented 
also  in  the  east— demonstrated  scrotal  gangrene,  enlarged  spleens,  and 
the  severely  darkened  rash  that  had  evoked  some  of  the  earliest  de- 
scriptions of  the  disease,  "black  measles"  and  "blue  disease."  In  con- 
trast, all  patients  in  whom  the  disease  lasted  more  than  twelve  days 
exhibited  brain  lesions,  more  pronounced  involvement  of  the  heart 
and  large  vessels,  and  a  tendency  toward  complications  such  as  bron- 
chopneumonia. Reiterating  a  point  from  S.  Burt  Wolbach's  19 19  paper, 
Lillie  emphasized  that  the  fundamental  lesion  in  spotted  fever  was 
found  in  the  circulatory  system,  where  Rickettsia  rickettsii  caused  the 
endothelial  cells  to  swell  and  even  burst,  resulting  in  occlusion  of  the 
small  vessels  or  promoting  the  formation  of  blood  clots.  Tersely  sum- 
ming up  a  decade  of  pathological  research,  Lillie  ended  the  debate  over 
the  differences  in  the  disease  east  and  west:  "It  may  be  concluded  that 
there  is  no  essential  difference  in  the  lesions  of  Rocky  Mountain  spotted 
fever  whether  in  the  Rocky  Mountain  area  or  on  the  eastern  seaboard 
of  the  United  States.""^^ 

Coincidently  with  these  laboratory  studies,  entomologists  were  ex- 
ploring a  new  tactic  to  control  tick  populations.  In  1930,  when  Emile 
Brumpt  identified  boutonneuse  fever  in  Marseilles,  he  had  recom- 
mended two  procedures  to  help  control  the  disease.  The  first  was  not 
unusual:  dogs  should  be  bathed  in  an  arsenical  solution  to  kill  ticks. 
Brumpt's  second  suggestion,  however,  was  aimed  at  achieving  biolog- 
ical control  of  ticks  by  exploiting  natural  host-parasite  relationships. 
For  some  years  he  had  studied  a  small  insect,  Ixodiphagus  caucurtei, 
which  burrowed  into  ticks  and  destroyed  them  from  the  inside.  He 
now  proposed  that  they  be  introduced  into  Marseilles  to  kill  ticks  by 
parasitizing  their  bodies. 

Brumpt's  idea  was  not  new— in  the  1880s  a  famous  and  successful 
experiment  in  biological  control  had  been  carried  out  in  California 
against  a  scale  insect  of  citrus  trees.  In  that  instance,  a  small  beetle 
imported  from  Australia  had  successfully  parasitized  the  scale  insect 
and  effected  complete  control  within  two  years.  Based  on  this  prec- 
edent, efforts  to  parasitize  ticks  had  already  been  tried  in  the  United 
States  with  mixed  success.  In  1926,  Wolbach  had  acquired  tick  par- 
asites from  Brumpt  to  experiment  with  biological  control  of  the  large 
dog  tick  population  that  plagued  summer  residents  of  islands  off  the 
Massachusetts  coast.  Released  on  the  islands  of  Naushon  and  Martha's 
Vineyard,  the  tick  parasites  survived  for  three  years,  but  their  numbers 
annually  diminished,  and  they  failed  to  become  established.  The  dif- 


Rocky  Mountain  Spotted  Fever 


ficulty  with  utilizing  such  natural  tick  control  methods  lay  in  the  fact 
that  these  insects  were  native  to  tropical  and  subtropical  areas  and 
did  not  thrive  in  colder  climates.  For  some  time,  however,  there  was 
hope  that  some  species  of  tick  parasites  might  be  adapted  to  the  north- 
ern United  States.  One  candidate  was  Hunterellus  hookeri,  prevalent 
in  Texas  and  commonly  called  the  chalcid  fly."*"^ 

In  Montana,  Robert  A.  Cooley  took  up  the  question  of  whether 
either  the  French  or  Texas  tick  parasite  could  be  used  to  reduce  the 
spotted  fever  tick  population.  In  July  1926  he  obtained  a  supply  of 
the  French  insects  from  Wolbach  and  later  received  Hunterellus  hookeri 
through  the  U.S.  Bureau  of  Entomology.  By  1928,  Cooley's  assistant 
at  the  Hamilton  laboratory.  Glen  Kohls,  had  reared  over  three  hundred 
thousand  of  the  French  parasites.  They  were  liberated  in  the  Bitterroot 
Mountains  to  see  if  they  would  parasitize  the  spotted  fever  tick  under 
natural  conditions. 

As  this  project  got  underway,  Cooley  laid  plans  to  travel  to  Africa, 
the  original  home  of  tick  parasites.  Believing  that  other  parasites  might 
yet  be  undiscovered,  Cooley  planned  to  search  for  new  ones  and  to 
learn  more  about  their  natural  habits.  In  1927  he  applied  to  the  Rocke- 
feller Foundation  for  funding  to  make  such  a  trip,  but  the  foundation 
rejected  the  proposal  as  falling  outside  the  narrow  medical  criteria  for 
which  they  gave  grants.  Cooley  raised  the  needed  funds  from  the 
Montana  State  Board  of  Entomology,  commercial  firms,  and  a  wealthy 
brother  in  New  York,  and  in  April  1928  he  sailed  for  Africa."^^ 

Although  Cooley  found  tick  parasites  in  the  province  of  Transvaal, 
South  Africa,  they  did  not  adapt  to  the  cold  Montana  climate  any 
better  than  the  French  species,  which  had  not  survived  the  winter  of 
1928-29  while  he  was  gone.  In  193 1,  when  Cooley  retired  from  uni- 
versity teaching  and  joined  the  Spotted  Fever  Laboratory  in  Fiamilton 
as  a  staff  entomologist,  he  began  experimenting  with  a  new  method 
known  as  latent  parasitism.  Previously  the  insects  had  been  released 
at  the  proper  time  to  attack  feeding  nymphal  ticks,  but  latent  parasitism 
called  for  releasing  the  insects  at  a  time  when  they  would  attack  larval 
ticks.  Theoretically,  the  parasites  remained  in  the  larvae  as  they  molted 
into  nymphs  and  there  overwintered  in  a  latent  condition.  Parasite 
development  proceeded  the  next  spring  when  nymphs  found  a  new 
host.  During  the  summer  of  1932,  Cooley  tried  this  method,  releasing 
Hunterellus  hookeri  parasites  in  Montana,  Idaho,  Oregon,  and  Col- 
orado. 

As  the  United  States  sank  deeper  into  the  Great  Depression,  Cooley 
waited  anxiously  for  the  spring  of  1933,  when  he  could  check  the 
results  of  his  work.  Curtailment  of  funds  prompted  by  the  Depression, 


spotted  Fever  outside  the  Rockies 


163 


however,  made  it  impossible  to  determine  the  results  of  these  releases, 
except  in  western  Montana.  These  restricted  studies  revealed  that  at 
least  some  of  the  parasites  had  survived  the  winter.  It  was  also  clear, 
however,  that  in  contrast  to  the  situation  in  tropical  climes,  only  one 
generation  of  parasites  each  year  was  likely  in  the  Rocky  Mountain 
area.'^^ 

By  1934  the  constraints  of  the  Depression  forced  an  end  to  the  tick 
parasite  experiments.  Cooley  had  showed  that  Hunterellus  hookeri 
could  survive  under  western  conditions  for  two  years  if  allowed  to 
overwinter  as  latent  parasites  in  unfed  nymphal  ticks.  The  work  had 
not,  obviously,  produced  the  hoped-for  effective  and  low-cost  means 
to  reduce  the  tick  population  that  carried  Rocky  Mountain  spotted 
fever.  Like  Lunsford  D.  Fricks's  abortive  sheep-grazing  theory,  how- 
ever, such  a  biological  control  system  would  have  been  a  triumph  had 
it  proved  workable.  In  1934,  Cooley  transferred  his  attention  to  an- 
other long-term  interest,  building  the  Spotted  Fever  Laboratory's  tick 
reference  collection.  In  1935  that  collection  contained  eighty-three 
identified  species  and  twenty-two  unidentified  species  of  ticks  from  all 
continents.'*^ 

The  end  of  the  tick  parasite  experiments  also  marked  the  beginning 
of  the  end  of  all  government-sponsored  tick  eradication  efforts  in  the 
Bitterroot  Valley.  State  and  county  appropriations  for  the  work  had 
already  been  drastically  reduced  during  the  Depression.  In  1935, 
A.  L.  Strand,  w^ho  had  succeeded  Cooley  in  193 1  as  secretary  of  the 
Montana  State  Board  of  Entomology,  called  a  meeting  with  the  U.S. 
PubHc  Health  Service,  the  U.S.  Bureau  of  Biological  Survey,  the  U.S. 
Forest  Service,  and  "other  interested  parties"  to  discuss  any  practical 
way  to  reduce  ticks  over  wide  areas  in  Montana.  Ralph  R.  Parker  and 
others  with  experience  in  tick  control  measures  offered  very  little  hope 
that  anything  would  work.  During  the  Depression,  men  in  the  Civilian 
Conservation  Corps  camps  in  the  Bitterroot  Valley  had  been  employed 
to  collect  ticks  and  assist  in  various  tick  control  efforts.  Parker  argued 
that  their  efforts  would  have  been  better  used  in  reforestation  of  mar- 
ginal land  on  the  western  edge  of  the  Bitterroot  Valley  next  to  the 
mountains.  After  this  meeting,  organized  tick  eradication  efforts  in 
western  Montana  were  suspended.  The  next  few  years  brought  ad- 
ditional checks  on  tick  parasites  and  occasional  bits  of  promising 
information  about  the  ability  of  the  insects  to  survive  in  cold  climates. 
Ground  squirrel  eradication  and  some  stock  dipping  were  continued 
by  individual  initiative,  but  no  further  attempt  was  made  to  eradicate 
ticks  from  mountainous  or  marginal  lands. ^° 

From  the  time  its  efficacy  was  first  demonstrated,  the  Spencer-Parker 


Rocky  Mountain  Spotted  Fever 


vaccine  was  embraced  throughout  the  west  as  the  principal  defense 
against  Rocky  Mountain  spotted  fever.  Because  of  the  pecuHar  nature 
of  this  tick  tissue  vaccine,  however,  long-term  funding  for  vaccine 
production  had  never  been  resolved.  The  U.S.  Public  Health  Service, 
which  had  funded  vaccine  development,  hoped  that  other  afflicted 
western  states  might  pool  resources  with  Montana  to  produce  it,  but 
all  such  requests  had  routinely  been  ignored.^ ^  As  demand  for  the 
vaccine  grew  outside  Montana,  the  state  thus  sought  to  shift  the  fiscal 
burden  for  future  vaccine  production  to  the  federal  government. 

Momentum  for  shifting  responsibihty  from  state  to  federal  shoulders 
increased  in  June  1930,  when  all  three  members  of  the  Montana  State 
Board  of  Entomology  attended  the  Salt  Lake  City  meeting  of  the 
western  branch  of  the  American  Public  Health  Association.  They  were 
successful  in  having  a  study  committee  appointed,  chaired  by  W.  F. 
Cogswell,  secretary  of  the  Montana  State  Board  of  Health  and  pres- 
ident of  the  state  board  of  entomology.  Comprised  of  the  state  health 
officers  of  Wyoming,  Idaho,  Arizona,  California,  and  Oregon,  the 
committee  met  in  Hamilton  on  24  September  1930  and  passed  a 
resolution  that  the  U.S.  Public  Health  Service,  through  a  congressional 
act,  should  take  over  the  work  of  the  Spotted  Fever  Laboratory,  in- 
cluding the  tick  parasite  research. 

The  following  month,  Cogswell  presented  the  resolution  to  the  na- 
tional meeting  of  the  association  in  Fort  Worth,  Texas.  The  president, 
A.  J.  Chesley,  made  particular  mention  of  the  spotted  fever  problem 
in  his  presidential  address,  and  Surgeon  General  Hugh  S.  Cumming 
of  the  U.S.  Public  Health  Service  called  a  luncheon  meeting  of  all  those 
interested  in  the  disease.  Since  one  case  of  spotted  fever  had  been 
reported  in  Texas  and  two  in  Nebraska,  Cumming  went  on  record  in 
support  of  Cogswell  by  stating  that  spotted  fever  was  a  national  prob- 
lem. After  this,  to  no  one's  surprise,  the  annual  meeting  adopted  the 
committee's  resolution.  Cogswell  followed  up  with  a  well-organized 
lobbying  campaign.  He  sent  out  a  circular  letter  to  all  state  health 
officers  seeking  support  for  the  legislation  and  for  an  adequate  ap- 
propriation. Thirty-nine  representatives  of  state  health  departments 
pledged  to  work  actively  in  the  effort.^^ 

On  Friday,  30  January  193 1,  Senator  T.  J.  Walsh  of  Montana  in- 
troduced S.  5959,  A  Bill  Authorizing  the  Purchase  of  the  State  Lab- 
oratory at  Hamilton,  Montana,  Constructed  for  the  Prevention,  Erad- 
ication, and  Cure  of  Spotted  Fever,  into  the  third  session  of  the  seventy- 
first  Congress.  In  a  speech  accompanying  the  introduction  of  the  bill, 
Walsh  emphasized  the  danger  of  vaccine  production  and  noted  the 
increased  demand  from  other  western  states.  New  York  Senator  Royal 


spotted  Fever  outside  the  Rockies 


165 


Copeland,  a  homeopathic  physician  with  a  strong  record  of  supporting 
pubhc  health  measures,  backed  Walsh,  citing  as  a  precedent  the  transfer 
of  the  quarantine  station  at  the  port  of  New  York  to  the  federal 
government.^"^ 

The  proposal  also  found  support  from  Senator  Hiram  Bingham  of 
Connecticut,  who  had  initiated  an  inquiry  about  vaccine  production 
at  the  urging  of  his  state  health  commissioner,  Stanley  H.  Osborn,  a 
member  of  Cogswell's  army  of  public  health  lobbyists.  Bingham  que- 
ried Treasury  Secretary  Andrew  Mellon,  in  whose  department  the  U.S. 
Pubhc  Health  Service  was  then  located,  about  support  for  the  Service's 
plans  to  take  action  against  spotted  fever.  The  senator  pointed  out  to 
Mellon  that  cases  known  outside  the  Rocky  Mountain  region  had  been 
traced  to  the  common  dog  tick,  Dermacentor  variabilis,  which  was 
plentiful  east  of  the  Mississippi  River  and  thus  a  potential  vector 
through  which  the  disease  might  spread.  Secretary  Mellon  replied  that 
he  had  already  approved  a  $35,620  increase  in  funds  for  spotted  fever 
work  in  fiscal  year  1932,  a  decision  that  augured  well  for  the  favorable 
consideration  of  Senator  Walsh's  bill.^^ 

As  was  customary  for  health-related  legislation,  Walsh's  bill  was 
referred  to  the  Senate  Commerce  Committee,  and  its  proponents 
stepped  up  their  lobbying  efforts.  Prominent  members  of  the  General 
Federation  of  Women's  Clubs  contacted  committee  members  and  other 
key  administration  officials.  Surgeon  General  Gumming  kept  a  tally 
of  letters  received  from  members  of  Congress  about  the  purchase  of 
the  laboratory.  In  addition  to  the  expected  letters  of  support  from 
western  states,  members  of  the  congressional  delegations  from  Ala- 
bama, Ohio,  Connecticut,  and  Maryland  all  wrote  to  praise  the  bill. 
Osborn  next  spurred  Bingham  into  soliciting  support  from  President 
Herbert  Hoover,  who  the  previous  year  had  demonstrated  an  interest 
in  public  health  matters  by  assisting  the  passage  of  a  U.S.  Public  Health 
Service  reform  act  and  the  Ransdell  Act  renaming  the  Hygienic  Lab- 
oratory the  National  Institute  of  Health.  Hoover  was  receptive,  and 
his  support  provided  the  leverage  needed  for  timely  and  favorable 
recommendations  from  the  Budget  Bureau  and  the  Treasury  Depart- 
ment, essential  requirements  for  the  passage  of  any  bill.^^ 

So  effective  was  the  work  of  the  organized  proponents  and  so  popular 
was  the  work  of  the  laboratory  that  only  one  incident  blemished  the 
bill's  forward  march  to  passage  in  the  Congress.  A  provision  for  Robert 
A.  Cooley's  tick  parasite  work  prompted  one  congressman  to  write  to 
the  secretary  of  agriculture,  asking  if  that  work  was  not  more  appro- 
priately done  under  the  auspices  of  the  U.S.  Bureau  of  Entomology. 
Echoing  the  decades-old  question  of  the  relation  between  professional 


mm'- 


spotted  Fever  outside  the  Rockies 


167 


entomologists  and  medical  researchers,  this  issue  arose  just  before  the 
bill  was  to  come  before  Congress.  Perhaps  lulled  by  the  generally 
favorable  response  to  the  bill,  Cooley  and  Ralph  R.  Parker  were  jarred 
by  the  news  that  the  tick  parasite  research  might  be  cut.  Parker  tele- 
graphed the  surgeon  general  that  the  Montana  state  legislature  had 
not  appropriated  additional  monies  for  entomological  work,  assuming 
that  the  U.S.  Public  Health  Service  would  take  it  over.  Assistant  Surgeon 
General  Lewis  R.  Thompson  replied  that  although  the  Service  had  not 
intended  to  take  up  the  work,  the  surgeon  general  would  allow  it  to 
be  funded  out  of  the  spotted  fever  appropriation  rather  than  see  it 
discontinued.  In  addition,  Thompson  intervened  with  the  secretary  of 
agriculture,  assuring  him  that  if  the  bill  passed,  there  would  be  no 
dispute  along  these  lines.  The  secretary,  settling  the  matter,  wrote  the 
inquiring  congressman  that  he  was  in  favor  of  the  passage  of  the  bill.^^ 

On  17  February,  two  weeks  after  its  introduction,  the  bill  was  re- 
ported favorably  out  of  committee  without  hearings  and  with  only 
two  minor  changes  in  its  language. Although  it  was  not  on  the  ap- 
proved calendar  of  the  Senate,  on  20  February,  Senator  Walsh  asked 
unanimous  consent  for  immediate  consideration  of  the  bill.  Unanimous 
consent  was  required  for  any  bill  not  already  scheduled,  and  since  the 
Senate  was  in  the  closing  days  of  its  session,  the  bill  would  have  been 
delayed  for  some  time  had  any  senator  objected.  Walsh  described  it 
as  "a  matter  of  very  great  importance  and  particular  urgency,"  noting 
that  its  consideration  should  not  lead  to  a  time-consuming  debate 
because  there  was  no  opposition.  Doubtless,  the  publication  that  very 
week  of  the  NIH  finding  that  spotted  fever  existed  in  Virginia  and 
along  the  eastern  seaboard  enhanced  the  Senate's  willingness  to  grant 
unanimous  consent.  The  bill  was  read,  the  amendments  accepted,  the 
bill  read  a  third  time  and  passed  without  a  recorded  vote.  On  27 
February  the  House  of  Representatives  approved  the  bill,  and  President 
Hoover  signed  it  on  2  March  as  Public  Law  No.  744.  Two  days  later, 
Hoover  also  signed  an  implementing  appropriations  act  that  authorized 
$150,000  for  spotted  fever  work  during  fiscal  years  193 1  and  1932.^^ 

Unfortunately,  this  legislation  was  enacted  just  as  the  Great  De- 
pression tightened  its  grip  on  the  United  States.  Within  a  year,  the 
effects  of  economic  calamity  became  everywhere  evident  in  federal 
programs.  "Sad  news  is  coming  from  Capitol  Hill,  daily,"  Roscoe  R. 
Spencer  wrote  to  Parker  in  March  1932.  "It  seems  our  salaries  will 
be  cut  inevitably  and  I  don't  know  what  is  going  to  happen  to  ap- 
propriations."^°  Spencer's  worst  fears  were  confirmed  in  early  1933, 
as  Frankhn  D.  Roosevelt  prepared  to  assume  the  presidency.  The 
budget  Roosevelt  inherited  from  Herbert  Hoover  proposed  a  reduction 


i68 


Rocky  Mountain  Spotted  Fever 


of  25  percent  for  the  U.S.  Public  Health  Service.  Rural  sanitation  work 
was  to  be  virtually  eliminated,  cut  from  $150,000  per  year  to  only 
$4,500,  and  the  Division  of  Mental  Hygiene's  budget  was  to  be  cut 
by  nearly  50  percent.  Research  programs  were  also  hard  hit.  Although 
the  maintenance  appropriation  of  the  NIH  was  slated  to  drop  only 
about  25  percent,  from  $54,775  to  $42,300,  "field  investigations" 
were  to  be  slashed  from  $3  53,564  to  only  $54,000.  This  broad  category 
covered  a  variety  of  research  programs  from  cancer  studies  in  coop- 
eration with  Harvard  University  to  research  on  scarlet  fever,  infantile 
paralysis,  and  sihcosis.  The  proposed  budget  also  eUminated  the  ap- 
propriation for  spotted  fever  work  and  stipulated  that  the  Hamilton 
laboratory  be  shut  down  and  the  vaccine  work  discontinued.^^ 

Surgeon  General  Gumming  countered  the  Treasury  Department's 
proposal  with  one  that  preserved  as  many  professional  positions  as 
possible  and  maintained  research  programs,  if  on  a  reduced  scale.  Of 
the  work  at  the  Spotted  Fever  Laboratory  he  wrote  to  Undersecretary 
of  the  Treasury  Arthur  A.  Ballantine: 

If  the  government  should  discontinue  this  activity  in  the  light  of  our  present 
knowledge,  the  persons  responsible  for  such  action  would  in  my  opinion  be 
morally  responsible  for  the  deaths  which  will  occur  as  a  result  of  the  lack  of 
this  material.  ...  I  may  add  that  only  a  few  days  ago  a"  request  was  received 
from  the  Army  for  a  large  quantity  of  this  material  to  be  used  for  the  protection 
of  its  forces  in  the  field.  The  Service  has  been  unable  to  persuade  any  other 
agency,  official  or  non-official,  to  undertake  the  preparation  of  this  material 
because  of  its  danger." 

Gumming  prevailed,  and  under  Roosevelt's  New  Deal  program,  there 
was  no  further  threat  to  the  laboratory's  existence. 

During  this  economically  constrained  period,  Ralph  R.  Parker  sought 
to  keep  his  small  group  of  researchers  in  the  mainstream  of  scientific 
research  by  adopting  practices  already  in  place  at  the  National  Institute 
of  Health.  He  initiated  monthly  staff  meetings  at  which  the  work  of 
each  scientist  was  discussed.  Recent  journal  literature  was  reviewed 
at  meetings  like  the  NIH's  long-established  Journal  Glub.^"^  Under 
Parker's  guidance,  the  laboratory  expanded  its  work  into  other  ar- 
thropod-borne diseases.  Growth  in  the  laboratory's  tick  reference  col- 
lection and  expertise  of  staff  entomologists  contributed  to  the  facility's 
fame  as  a  center  for  diseases  of  nature.  In  the  1933  outbreak  of  en- 
cephalitis in  Saint  Louis,  Missouri,  and  the  1935  discovery  of  bubonic 
plague  in  rodents  near  Dillon,  Montana,  entomological  experts  from 
the  laboratory  cooperated  with  U.S.  Public  Health  Service  physicians 
in  identifying  the  arthropod  vectors  and  devising  means  to  control  the 
diseases. 


spotted  Fever  outside  the  Rockies 


169 


Tularemia,  which  had  first  been  recognized  as  a  problem  in  the 
laboratory  animals  used  to  test  spotted  fever  vaccine,  became  another 
disease  of  nature  in  which  laboratory  staff  developed  expertise.  Re- 
search in  the  early  1930s  indicated  that,  in  contrast  to  what  had  been 
believed,  mild  strains  of  tularemia  could  be  demonstrated  in  nature. 
The  laboratory  experimentally  secured  mechanical  transmission  of  the 
disease  with  the  deer  fly  and  black  fly  and  demonstrated  that  the  feces 
of  some  arthropods  were  infective.  In  1934,  two  entomologists,  Cor- 
nehus  B.  Philip  and  William  L.  Jellison,  investigated  an  epizootic  of 
tularemia  among  sheep  near  RingHng,  Montana.  Curiously,  none  of 
the  ranch  employees  became  infected,  even  though  they  hand-picked 
ticks  from  sheep  and  skinned  those  that  died.^^ 

Two  other  newly  discovered  tick-borne  diseases  were  also  investi- 
gated at  the  laboratory.  Tick  paralysis,  a  mysterious  disease  that  par- 
alyzed a  victim's  motor  nerves,  was  found  to  be  caused  only  by  the 
bite  of  the  female  wood  tick,  Dermacentor  andersoni.  Believed  to  be 
caused  by  a  toxin,  the  paralysis  began  in  the  legs  and  slowly  ascended. 
If  the  tick  was  not  removed  before  the  paralysis  reached  the  respiratory 
muscles,  the  patient  died.  Once  the  tick  had  been  removed,  however, 
the  patient  recovered  rapidly.  In  1926  a  report  received  from  Colorado 
launched  a  study  of  a  disease  that  came  to  be  called  Colorado  tick 
fever.  By  the  early  1930s  this  tick-borne  infection  could  be  character- 
ized only  as  "a  probable  disease  entity,"  but  continuing  reports  con- 
firmed it  as  a  viral  malady  having  symptoms  similar  to  those  of  spotted 
fever  with  a  shorter,  milder  course  and  no  rash.  Usually  there  were 
two  distinct  periods  of  fever  separated  by  a  symptomless  day  or  two.^^ 

In  addition  to  these  investigations,  researchers  at  the  Spotted  Fever 
Laboratory  discovered  an  entirely  new  rickettsial  disease.  During  the 
summer  of  1935,  Gordon  E.  Davis,  a  bacteriologist,  isolated  a  filter- 
passing  agent  from  Dermacentor  andersoni  ticks  brought  in  by  a  lab- 
oratory attendant,  Lawrence  Humble,  in  connection  with  the  tick- 
collecting  work  of  the  Civilian  Conservation  Corps  (CCC)  camp  near 
Nine  Mile,  Montana.  The  following  year  a  similar  agent  was  also 
found  in  D.  occidentalis  ticks  from  southwest  Oregon,  Cahfornia,  and 
British  Columbia.  Initial  investigation  suggested  that  it  caused  a  disease 
of  wild  animals,  but  in  March  1936,  Parker  wrote  the  surgeon  general 
that  he  and  Davis  were  practically  certain  that  the  organism  was  the 
agent  of  a  disease  in  man.  This  new  malady,  which  caused  headache, 
high  fever,  body  aches  and  pains— in  short,  all  the  symptoms  of  known 
rickettsial  diseases  except  for  a  widespread  rash— was  soon  designated 
Nine  Mile  fever,  and  Herald  R.  Cox,  a  newly  arrived  bacteriologist 
whose  work  will  be  discussed  more  thoroughly  in  the  chapter  9,  took 


Rocky  Mountain  Spotted  Fever 


up  the  study  of  the  causative  agent.  By  1938,  Davis  and  Cox  had 
pubhshed  a  description  of  their  work  on  this  mysterious  agent,  and 
Cox  went  on  to  characterize  it  as  a  rickettsia,  for  which  he  suggested 
the  name  Rickettsia  diaporica.^^  This  new  organism,  it  was  discovered, 
was  present  in  many  lots  of  the  Spencer-Parker  vaccine,  hence  vaccine 
recipients  were  unwittingly  inoculated  against  Nine  Mile  fever  as  well. 
Since  the  laboratory  believed  its  vaccine  to  be  free  from  contaminating 
organisms,  however,  this  discovery  caused  great  concern. 

The  year  before  Davis  and  Cox  pubhshed  their  description  of  the 
organism,  in  a  twist  of  scientific  fate,  an  AustraHan  physician,  Edward 
Holbrook  Derrick,  published  an  account  of  a  mysterious  disease  with 
similar  symptoms  occurring  among  abattoir  workers  in  Queensland. 
Derrick  designated  it  Q  fever,  the  Q  for  "query,"  since  little  was  then 
known  about  the  illness.  His  countryman  and  a  distinguished  virol- 
ogist, Frank  Macfarlane  Burnet,  swiftly  identified  the  agent  as  a  rick- 
ettsia. By  the  end  of  the  decade,  investigators  on  both  sides  of  the 
Pacific  had  confirmed  that  the  two  diseases  were  identical.  The  priority 
of  the  AustraHan  name  Q  fever  supplanted  the  designation  Nine  Mile 
fever  for  this  disease,  which  later  was  found  to  exist  around  the  globe. 
When  the  Q  fever  organism  was  classed  as  a  separate  genus  from  other 
rickettsia,  it  was  named  Coxiella  burnetii  after  Cox  and  Burnet  who 
had  initially  described  \t7^ 

Such  productive  research  at  the  Spotted  Fever  Laboratory  during 
the  Depression  years  was  clearly  secondary  to  and  protected  by  the 
demonstratively  useful  production  of  Rocky  Mountain  spotted  fever 
vaccine. During  the  early  1930s,  the  greatest  demand  for  the  vaccine 
came  from  the  Bitterroot  Valley  and  from  Harney  County,  Oregon. 
In  193  3  requests  for  the  vaccine  increased  considerably  from  the  eastern 
states,  and  the  laboratory  forwarded  approximately  10,500  cc  to  the 
NIH  for  distribution  on  the  east  coast.  In  addition,  vaccine  was  needed 
by  the  CCC  camps  in  western  national  forests.  Because  demand  for 
the  vaccine  always  outstripped  supply,  the  U.S.  Public  Health  Service 
ruled  that  the  civilian  population  was  entitled  to  first  consideration. 
Only  the  Bitterroot  Valley  CCC  camps  were  certain  to  receive  the 
vaccine.  To  mitigate  this  problem,  the  corps  allocated  special  funds  in 
December  1933,  and  CCC  personnel  in  the  Bitterroot  flagged  ticks  for 
the  extra  batch  of  vaccine.  Since  adult  ticks  alone  were  used,  the  yield 
was  low:  only  40.8  liters  out  of  123  produced  met  potency  standards. 
Even  so,  this  amount  was  adequate  to  protect  personnel  in  all  highly 
infected  areas  of  the  west.^^ 

In  December  1934  this  tenuous  situation  was  strained  when  news- 
papers reported  that  the  president  might  double  the  number  of  men 


spotted  Fever  outside  the  Rockies 


Demand  for  the  Spencer-Parker  vaccine  always  outstripped  supply.  Here 
bottles  of  vaccine  await  shipment,  resting  on  orders  in  letters  and  telegrams 
from  across  the  United  States.  (Courtesy  of  the  Rocky  Mountain 
Laboratories,  NIAID.) 


in  the  CCC  camps.  By  April  1935  ^^e  rumor  had  become  fact.  Nearly 
two  hundred  new  camps  were  scheduled,  including  two  in  the  Bitter- 
root  and  a  number  of  others  near  the  northern  Rocky  Mountain  spotted 
fever  region  where  the  need  for  vaccine  was  most  urgent.  Parker  feared 
that  the  vaccine  supply  would  be  severely  strained  by  these  develop- 
ments, especially  since  the  laboratory's  budget  never  seemed  secure. 
For  fiscal  year  1934,  for  example,  the  appropriation  had  initially  been 
cut  from  $86,649  to  $49,000.  Eventually,  an  additional  $17,000  was 
released,  and  the  CCC  had  contributed  $20,000  toward  the  special 
lot  of  vaccine  for  the  camps.  In  fact,  the  growing  demand  from  the 
corps  probably  helped  to  stabilize  the  laboratory's  budget.  For  fiscal 
19355  $71,000  was  allocated,  with  an  additional  $20,000  expected 
from  the  CCC.^^ 

Many  western  citizens  also  complained  directly  to  their  congressmen 
about  inadequate  appropriations  for  vaccine  work,  often  prodded  by 
newspaper  reporters,  who  were  always  prepared  to  question  the  pri- 
orities of  government.^"^  This  rising  demand  for  the  Spencer-Parker 
vaccine  was  carefully  documented  by  Ralph  R.  Parker,  who  attached 
copies  of  many  of  the  letters  to  his  monthly  reports  to  the  surgeon 
general.  A  physician  in  Prineville,  Oregon,  Parker  noted,  penned  the 
following  plea:  "Can  you  let  me  have  any  amount  of  serum?  Ticks 


172 


Rocky  Mountain  Spotted  Fever 


awful  bad  and  people  panicky.  Send  if  possible."  Many  isolated  farmers 
and  ranchers  also  earnestly  sought  the  vaccine.  "We  are  50  miles  from 
the  nearest  Doctor  .  .  .  and  each  time  we  ask  there,  they  are  always 
out  of  this  serum  and  in  the  rare  instances  when  some  of  our  neighbors 
have  been  able  to  get  it,  the  charge  is  $2.00  each,"  wrote  R.  S.  Mefford 
from  Decker,  Montana. Nurses  and  druggists  also  requested  vaccine 
to  administer  to  persons  far  distant  from  physicians.  Their  pleas  were 
in  vain,  because  laboratory  policy  restricted  vaccine  distribution  to 
physicians  and  state  or  local  health  authorities. 

In  part,  this  policy  was  adopted  to  assure  that  vaccine  recipients 
would  be  supervised  by  a  physician  in  the  event  of  untoward  side 
effects,  with  the  additional  benefit  that  statistics  on  the  vaccine's  ef- 
fectiveness would  be  easy  to  collect.^^  U.S.  Public  Health  Service  policy 
was  also  influenced  by  the  widely  prevailing  philosophy  of  the  medical 
profession  in  the  United  States.  Championed  by  the  AMA,  this  view 
held  that  physicians  alone  should  administer  all  such  vaccines  and 
collect  a  fee  for  the  service  from  all  who  were  able  to  pay.^^  The  vaccine 
itself  was  suppHed  by  the  laboratory  at  no  charge. 

Bitterroot  Valley  residents  especially  resented  this  policy  in  1935, 
when  they  were  asked  to  pay  for  the  vaccine  after  ten  years  of  receiving 
it  free  while  the  Service  tested  its  efficacy.  A.  C.  Baker  of  Hamilton 
complained  to  Montana  Senator  B.  K.  Wheeler  that  "the  poor  people 
of  this  valley"  should  continue  to  be  vaccinated  at  no  cost.  "You  take 
a  poor  family  that  has  from  six  to  10  children,  to  pay  $1.00  per  child 
would  be  a  serious  hardship.  The  consequences  will  be,  that  they  will 
not  take  the  vaccine  and  then  you  will  see  the  death  list  grow  this  year 
from  the  spotted  fever."  Responding  to  the  senator's  inquiry  about 
the  matter,  Parker  noted  that  the  Service  had  actually  planned  to 
discontinue  free  vaccinations  in  1933  but  "because  of  the  general 
existing  financial  situation,"  free  vaccinations  had  been  continued  for 
two  additional  years.  He  also  pointed  out  that  valley  residents  could 
travel  to  Missoula  and  receive  the  vaccine  free  from  the  county  health 
officer  and  that  local  physicians  in  Ravalli  County  were  scaling  their 
fees  and  vaccinating  without  charge  "the  families  of  those  who  are  on 
relief."  Other  Montana  counties  offered  free  health  department  cHnics, 
also,  and  during  the  1940s,  the  Ravalli  County  health  department 
instituted  such  a  program. 

Other  groups  willing  to  pay  a  fee  if  only  they  could  obtain  the 
vaccine  included  physicians  and  hospital  associations  representing  con- 
struction companies  with  large  crews  of  men  working  in  the  field. 
Because  of  the  limited  amount  of  vaccine,  Parker  resisted  sending  lots 
to  these  people,  believing  that  it  was  being  used  "to  decrease  com- 


spotted  Fever  outside  the  Rockies 


173 


pensation  costs  for  construction  companies  employing  common  la- 
bor."^^  Parker  finally  asked  the  Service  for  guidelines  on  how  the  limited 
supply  of  vaccine  should  be  allocated.  Taking  a  somewhat  more  liberal 
view,  Assistant  Surgeon  General  Lewis  R.  Thompson,  chief  of  the 
Scientific  Research  Division,  summarized  the  Service's  rationale: 

I  believe  the  first  principle  that  should  concern  us  is  to  get  the  vaccine  into 
the  more  dangerous  areas  first.  Requests  from  such  areas  should  be  filled  to 
a  greater  extent  than  in  the  less  dangerous  areas.  Second,  I  believe  that  the 
people  who  deserve  the  first  consideration  are  those  whose  work  takes  them 
into  dangerous  areas.  I  do  not  believe  the  city  man  has  the  same  call  upon  us 
as  the  country  man,  even  if  he  has  a  now  and  then  exposure.  Third,  I  do  not 
think  that  we  should  favor  Federal  employees,  although  I  can  see  that  here 
and  there  you  may  find  individuals  or  groups  which  have  as  much  right,  by 
reason  of  the  nature  of  their  work,  as  civilians.  Fourth,  I  believe  that  the 
question  of  decreasing  compensation  hazards  for  construction  companies 
should  not  be  taken  into  consideration  but  that  such  cases  should  be  weighed 
in  the  same  manner  as  all  others. ^° 

Fortunately  for  Parker,  who  remained  the  principal  person  besieged 
with  pleas  for  more  vaccine,  empirical  experience  with  vaccine  pro- 
duction over  the  years  had  led  to  many  improvements  that  increased 


TABLE  3.  Production  of  Spencer-Parker  Vaccine,  19Z8-1940 


Year 

Liters  (gross) 

Liters  (net) 

1928 

12.8 

* 

1929 

25.2 

* 

1930 

55.0 

* 

1931 

117.2 

* 

1932 

153.2 

* 

1933 

205.1 

* 

1934 

212 

171 

1935 

315.6 

248.4 

1936 

506.8  (360)** 

274 

1937 

591.2  (309.6)** 

462.4 

1938 

592.4 

362.9 

1939 

756 

495 

1940 

559 

515 

SOURCE:  RML,  Annual  Reports,  1928-40. 

NOTES:  The  widest  use  of  the  vaccine  was  during  this  period.  After  1940,  both  tick  tissue  and 
yolk  sac  vaccine  were  produced.  Tick  tissue  vaccine  was  temporarily  discontinued  during  World 
War  II  and  never  returned  to  prewar  levels.  In  1948,  when  Lederle  Laboratories  began  producing 
yolk  sac  vaccine  commercially,  produaion  of  tick  tissue  vaccine  ceased. 

*  Information  not  given 

**In  1936  the  laboratory  began  storing  a  portion  of  vaccine  for  use  in  future  years.  The  figures 
given  in  parentheses  represent  the  number  of  liters  used  during  the  year  that  were  also  manufactured 
during  that  year. 


174 


Rocky  Mountain  Spotted  Fever 


the  volume  available  for  distribution.  These  advances,  which  v^^ere 
noted  in  chapter  7,  enabled  the  laboratory  to  produce  205.1  liters  of 
vaccine  by  1933,  an  increase  of  3,600  percent  over  the  tiny  amount 
produced  in  1926,  the  first  year  in  v^hich  vaccine  production  had  been 
attempted  (see  Table  3  for  a  summary  of  liters  produced,  1928-40).^^ 
Another  major  step  forward  was  the  1935  discovery  that  vaccine  could 
be  stored  without  loss  of  potency,  thus  allowing  some  reserve  stock 
to  be  maintained.  Even  with  such  improvements,  the  process  remained 
expensive.  Each  liter  of  the  vaccine  cost  about  $375  to  produce. 

Although  the  Spencer-Parker  vaccine  was  embraced  by  thousands 
of  people  as  the  only  hope  against  Rocky  Mountain  spotted  fever, 
Ralph  R.  Parker  and  the  NIH  typhus  unit  continued  to  search  for  a 
simpler,  less  dangerous,  and  cheaper  method  of  vaccine  preparation. 
The  discovery  that  spotted  fever  existed  in  the  eastern  United  States 
and  in  South  America  underscored  the  national  and  international  sig- 
nificance of  this  quest.  After  the  U.S.  Public  Health  Service  assumed 
full  responsibility  for  producing  spotted  fever  vaccine,  the  burden  of 
developing  any  new  method  rested  on  its  investigators.  Although  the 
Great  Depression  hindered  an  all-out  attack  on  the  problem,  research 
at  last  proved  fruitful.  The  discovery  of  this  improved  method  and  its 
broad  applications  to  rickettsial  disease  research  are  the  subjects  to 
which  we  now  turn. 


Chapter  Nine 


Dr.  Cox's  Versatile  Egg 

An  active  field  of  science  is  like  an  immense  anthill;  the  individual  almost 
vanishes  into  the  mass  of  minds  tumbling  over  each  other,  carrying 
information  from  place  to  place,  passing  it  around  at  the  speed  of  light. 

Lewis  Thomas,  The  Lives  of  a  Cell 


Rearing  millions  of  ticks  each  year  and  converting  them  into  Rocky 
Mountain  spotted  fever  vaccine  v^as  a  service  for  w^hich  residents  of 
infected  areas  w^ere  profoundly  grateful.  Numerous  people  who  grew^ 
up  in  Montana  during  the  1920s  and  1930s  recall  Wixh  wry  affection 
the  sore,  red  arms  they  dutifully  endured  each  year  in  order  to  be 
protected  from  the  dread  disease.^  The  danger,  expense,  and  sheer 
awkwardness  of  making  vaccine  out  of  ground-up  ticks,  however, 
weighed  heavily  on  laboratory  staff  members.  Toward  the  end  of  the 
1930s,  a  new  method  for  preparing  spotted  fever  vaccine  was  developed 
that  also  proved  applicable  to  other  rickettsial  diseases.  It  also  per- 
mitted the  development  of  a  more  discriminatory  diagnostic  test  and 
opened  the  way  to  fundamental  studies  on  rickettsial  organisms.  The 
discovery  of  this  technique  was  informed  by  productive  research  on 
the  filterable  viruses,  and  its  subsequent  applications  were  hastened 
by  the  medical  problems  of  World  War  II. 

It  was  clear  that  the  key  to  a  better  vaccine  was  finding  some  medium 
other  than  ticks  in  which  rickettsiae  would  thrive.  The  relatively  new 
method  of  tissue  culture  held  great  promise  for  solving  the  problem. 
In  this  technique,  small  fragments  of  tissue,  such  as  minced  chick 
embryo,  were  placed  in  plasma,  serum,  or  some  other  "natural"  me- 
dium enhanced  with  nutrients.  Strict  asepsis  was  needed  to  prevent 
contamination,  but,  if  properly  maintained,  the  tissue  culture  would 
grow  and  could  be  inoculated  with  microorganisms  known  to  multiply 
in  the  cultured  cells.  Because  the  nourishing  media  and  the  tissues  often 
varied  in  composition,  however,  quantitative  control  was  extremely 
difficult  to  maintain.^  In  1923,  S.  Burt  Wolbach  and  M.  J.  Schlesinger 
at  Harvard  University  experimented  with  tissue  plasma  cultures  and 
were  able  to  keep  rickettsiae  alive  for  four  generations.^  Unfortunately, 


175 


Rocky  Mountain  Spotted  Fever 


Ida  A.  Bengtson,  the  first  woman 
on  the  professional  staff  at  the 
Hygienic  Laboratory  of  the  U.S. 
Pubhc  Heahh  Service, 
investigated  ahernative  methods 
for  producing  spotted  fever 
vaccine.  In  1937  she  reported 
that  an  acceptable  vaccine  could 
be  produced  with  rickettsiae 
grown  in  tissue  cultures.  Her 
technique  was  shortly  eclipsed  by 
Herald  R.  Cox's  simpler  method 
of  cultivating  rickettsiae  in  fertile 
hens'  eggs.  (Courtesy  of  the 
National  Library  of  Medicine.) 


the  vaccine  process  required  much  more  luxuriant  grov^th  of  the  rick- 
ettsiae than  the  developing  technique  was  able  to  produce. 

A  much  simpler  technique  for  cultivating  the  filterable  viruses  v^as 
discovered  in  193 1  by  Alice  Miles  Woodruff  and  Earnest  Goodpasture 
at  Vanderbilt  University.  They  found  that  the  chorioallantoic  mem- 
brane of  the  developing  chick  embryo  provided  an  ideal  medium  for 
the  growth  of  the  fowl  pox  virus.  This  membrane  is  one  of  several  in 
chick  embryos;  the  amniotic  and  yolk  sac  membranes  are  two  others. 
The  chorioallantoic  membrane  is  located  just  beneath  the  shell  of  the 
egg,  hence  it  was  easy  to  inoculate  and  to  observe  any  growth  of  the 
pathogen  that  occurred.  Soon  after  Woodruff  and  Goodpasture  an- 
nounced their  method,  other  researchers  identified  a  number  of  viruses 
that  flourished  on  this  membrane."* 

At  the  National  Institute  of  Health,  a  senior  bacteriologist,  Ida  A. 
Bengtson,  joined  the  typhus  unit  specifically  to  explore  various  methods 
of  cultivating  Rocky  Mountain  spotted  fever  organisms.  Having  be- 
come the  first  woman  on  the  staff  of  the  Hygienic  Laboratory  in  1916, 
Bengtson  completed  work  for  a  Ph.D.  in  bacteriology  in  19 19  at  the 
University  of  Chicago.^  Before  taking  up  work  on  the  spotted  fever 
problem,  she  had  distinguished  herself  in  studies  of  anaerobic  bacteria 
and  the  toxins  they  produced.  She  also  identified  a  new  variety  of 
Clostridium  botulinum,  which  caused  a  disease  known  as  "limber- 


Dr.  Cox's  Versatile  Egg 


^77 


neck"  in  chickens,  and  studied  the  etiology  of  trachoma,  an  eye  disease 
whose  causative  agent  was  then  suspected  to  be  a  rickettsia.  In  1935, 
Bengtson  and  Rolla  E.  Dyer  began  experimenting  with  the  Woodruff 
and  Goodpasture  technique.  They  eventually  managed  to  cultivate 
spotted  fever  rickettsiae  on  the  chorioallantoic  membrane  of  chick 
embryos,  but  the  stubborn  organisms  refused  to  grow  in  the  quantities 
necessary  for  vaccine  preparation.^ 

After  these  disappointing  results,  Bengtson  turned  back  to  standard 
tissue  culture  techniques,  studying  the  results  other  investigators  had 
achieved  with  a  variety  of  tissue  types.  The  combination  that  worked 
best,  she  found,  contained  modified  Maitland  media,  minced  chori- 
oallantoic membrane,  and  guinea  pig  tunica  vaginaHs,  the  scrotal  mem- 
brane in  which  rickettsiae  were  concentrated.  Shortly  thereafter,  she 
reported  that  a  vaccine  could  be  made  from  spotted  fever  rickettsiae 
cultivated  in  this  manner.  "The  amount  of  vaccine  which  may  be 
prepared  is  sufficient  to  suggest  this  method  of  preparation  as  prac- 
ticable."" 

Bengtson's  method,  although  not  ideal,  might  have  supplanted  the 
tick  tissue  method,  had  not  a  serendipitous  discovery  intervened  to 
revolutionize  the  preparation  of  all  types  of  rickettsial  vaccines.  Before 
this  scientific  breakthrough  is  discussed,  however,  a  digression  is  nec- 
essary to  examine  the  political  context  in  which  it  occurred,  because 
this  particular  discovery  might  not  have  come  so  soon,  if  ever,  without 
the  beneficial  stimulation  of  President  Franklin  D.  Roosevelt's  New 
Deal  program.  In  1935,  just  as  Bengtson  was  beginning  her  work, 
Roosevelt's  activist  social  planners  were  guiding  the  wide-ranging  So- 
cial Security  Act  through  Congress.  Signed  into  law  in  August,  the  act 
not  only  provided  for  old  age  assistance  and  other  welfare  measures 
but  also  authorized  the  expenditure  of  large  sums  for  public  health 
work.^  Title  VI  provided  $2  miUion  annually  for  health  research  in 
the  U.S.  Pubhc  Health  Service.  This  intersection  of  public  policy  and 
medical  research  stimulated  the  work  of  federal  investigators.  They 
could  purchase  new  equipment,  undertake  new  projects,  and,  perhaps 
most  importantly,  hire  young  researchers  for  the  first  time  since  the 
Great  Depression  began. 

Passage  of  Social  Security  was  anticipated  with  relish  in  the  U.S. 
Public  Health  Service  for  some  months  before  Congress  voted  on  it. 
Inviting  suggestions  for  ways  to  expand  research  must  have  been  pleas- 
ant indeed  for  Service  leaders,  who  had  endured  years  of  diminished 
budgets.  In  March  1935  Assistant  Surgeon  General  Lewis  R.  Thomp- 
son, director  of  the  Division  of  Scientific  Research,  received  from  Ralph 
R.  Parker  a  long  list  of  research  projects  that  would  be  worthy  of 


178 


Rocky  Mountain  Spotted  Fever 


funding  at  the  Spotted  Fever  Laboratory.  An  ambitious  $17,540  com- 
parative study  of  typhus-like  diseases  was  first  on  Parker's  '  Vish  Hst," 
follow^ed  by  an  allocation  of  $9,000  to  "study  methods  of  improving 
the  present  spotted  fever  vaccine  and  to  seek  some  simpler  method  of 
vaccine  production."^ 

Enactment  of  Social  Security  also  presaged  major  changes  in  the 
U.S.  Public  Health  Service.  Hugh  S.  Gumming,  who  had  served  as 
surgeon  general  since  1920,  found  President  Roosevelt's  New  Deal 
more  liberal  than  his  personal  conservative  philosophy  could  support. 
In  1936  he  retired  and  was  replaced  by  Thomas  Parran,  who,  during 
Roosevelt's  tenure  as  governor  of  New  York,  had  been  granted  leave 
from  the  Service  to  become  New  York  state  health  officer.  In  1937, 
Parran  reorganized  the  research  program  of  the  Service,  consolidating 
the  Division  of  Scientific  Research  with  the  National  Institute  of  Health. 
As  a  result,  NIH's  longtime  director,  George  W.  McGoy,  who,  Hke 
Gumming,  was  a  conservative,  was  replaced  by  Lewis  R.  Thompson, 
director  of  the  Division  of  Scientific  Research  and  a  strong  New  Deal 
supporter. 

In  Montana  the  most  noticeable  change  during  this  period  was  the 
laboratory's  new  name.  Through  January  1936  the  faciHty  was  known 
popularly  as  the  Spotted  Fever  Laboratory  and  officially  as  the  Ham- 
ilton Station  of  the  U.S.  Public  Health  Service.  In  February  it  became 
the  Rocky  Mountain  Laboratory  (RML).^^  Soon  other  traditional  cus- 
toms also  disappeared.  Parker  had  always  prefaced  his  monthly  reports 
to  the  surgeon  general  with  the  phrase  "I  have  the  honor  of  submitting," 
after  which  he  surveyed  general  topics,  often  commented  on  personnel 
and  on  additions  to  the  physical  plant,  and  finally  focused  on  specific 
research  activities.  By  1938  the  older  formalities  and  the  highly  per- 
sonal form  of  monthly  reports  gave  way.  Personnel  and  facilities  reports 
were  filed  separately,  and  the  monthly  reports  contained  streamlined 
summaries  of  research  projects. 

Most  importantly  for  the  spotted  fever  research  program,  the  Title 
VI  provisions  of  the  Social  Security  Act  enabled  the  Service  to  hire 
Herald  R.  Gox,  a  microbiologist  whose  primary  duty  was  to  search 
for  a  less  dangerous,  more  efficient  means  to  produce  spotted  fever 
vaccine.  Born  on  28  February  1907  in  Rosedale,  Indiana,  Gox  took 
his  undergraduate  degree  at  Indiana  State  Gollege  in  1928  and  earned 
a  Doctor  of  Science  degree  in  193 1  at  Johns  Hopkins  University  with 
research  in  the  filterable  viruses. From  1932  to  1936  he  was  an 
assistant  in  Peter  K.  Olitsky's  laboratory  at  the  Rockefeller  Institute, 
where,  according  to  one  eminent  virologist,  Gox  "got  a  wonderful 


Dr.  Cox's  Versatile  Egg 


179 


In  1937  Herald  R.  Cox  discovered  that  rickettsiae  would  grown  luxuriantly 
in  the  yolk  sacs  of  fertile  hens'  eggs.  This  discovery  revolutionized  the 
production  of  Rocky  Mountain  spotted  fever  vaccine.  It  also  provided  a 
means  to  produce  vaccines  against  epidemic  typhus  and  other  rickettsial 
diseases.  (Courtesy  of  the  Rocky  Mountain  Laboratories,  NIAID.) 

training  in  doing  experimental  work  with  various  viruses."  He  reported 
for  duty  at  Hamilton  on  31  May  1936.^^ 

For  "the  better  part  of  two  years,"  Cox  experimented  with  flask 
cultures  of  tissues  derived  from  chicken  embryos  and  chorioallantoic 
membranes.  He  used  a  variety  of  nutrient  media,  "without  a  bit  of 
worthwhile  success."  After  offering  his  resignation  to  Parker  and  being 
told  to  keep  trying.  Cox  had  one  of  those  happy  accidents  of  science 
that  solved  the  problem.  In  late  February  1938  he  temporarily  ran  out 
of  the  chorioallantoic  membrane  and  embryonic  chicken  tissues  needed 
to  conduct  one  experiment  properly.  What  he  had  immediately  avail- 
able, however,  was  yolk  sac  membrane  tissue,  aseptically  removed  and 
stored  in  an  Erlenmeyer  flask.  In  order  to  proceed  with  his  plans,  he 


i8o 


Rocky  Mountain  Spotted  Fever 


inoculated  the  yolk  sac  tissue  with  rickettsiae.  Within  a  week,  Cox 
found  "literally  thousands"  of  rickettsiae  growing  in  the  yolk  sac 
cultures.  "That  night  I  was  too  excited  to  sleep,"  he  recalled  in  a  later 
memoir.  His  mind  racing,  he  realized  that  flask  culture  was  unnec- 
essary. "It  would  be  so  much  simpler  to  inoculate  fertile  hens'  eggs 
directly  into  the  yolk  sac  area,  through  the  air  sac  end  of  the  egg,"  he 
reasoned.  Since  he  lived  close  to  the  laboratory,  Cox  decided  to  try 
this  new  idea  immediately.  At  four  o'clock  that  morning,  he  went  back 
to  the  laboratory  and  inoculated  the  first  yolk  sacs  directly  through 
the  egg  shell. 

After  several  repetitions  of  the  experiment  with  uniformly  successful 
results.  Cox  reported  the  breakthrough  via  the  laboratory's  April 
monthly  report.  When  the  news  reached  the  NIH  in  Bethesda,  however, 
RoUa  E.  Dyer  was  apparently  not  convinced.  With  some  reHsh,  Cox 
recounted  Dyer's  trip  to  Montana  to  inspect  the  new  procedure. 

Dr.  Dyer  came  into  the  lab  at  about  1:30  p.m.  It  was  the  first  time  we  had 
ever  met,  and  I  soon  learned  that  he  was  one  that  came  immediately  to  the 
point  in  his  speech  and  did  not  stand  for  any  monkey  business.  The  first  thing 
that  Dr.  Dyer  said  to  me  was,  "Cox,  I  don't  believe  a  damned  word  in  that 
recent  monthly  report  of  yours,  in  which  you  state  that  you  are  able  to  cultivate 
rickettsiae  in  great  numbers  in  fertile  hens'  eggs,  because  Dr.  Ida  Bengtson 
and  I  tried  for  about  3  years  to  grow  rickettsiae  in  fertile  hens'  eggs  and  we 
didn't  have  a  bit  of  luck."  I  said,  "Dr.  Dyer,  did  you  ever  examine  the  yolk 
sac  membrane  tissue  in  those  eggs  to  see  if  any  rickettsiae  were  there?"  He 
said,  "No,  we  didn't."  I  said,  "Well,  that  was  your  mistake,  because  that  is 
where  you  would  find  the  rickettsiae.  Now,  let's  quit  arguing  and  you  sit  down 
and  look  at  these  representative  slides  of  spotted  fever,  epidemic  typhus  and 
Nine  Mile  fever,  and  then  tell  me  what  you  think  of  them."  Well,  Dr.  Dyer 
sat  down  and  looked  at  slides  for  about  lo-i  5  minutes.  Then  he  turned  around 
and  said,  "Well,  I'll  be,  but  you've  convinced  me.  You  surely  have  done  what 
you  stated  you  did."  Then  he  stood  up  and  shook  my  hand,  as  if  to  seal  the 
bargain. 

It  is  difficult  to  overstate  the  impact  of  Cox's  discovery  on  every 
area  of  rickettsial  disease  research  during  the  next  decade.  As  soon  as 
he  published  his  method,  it  was  apparent  that  the  long-sought  means 
had  been  found  to  cultivate  all  types  of  rickettsial  organisms  not  only 
easily  but  cheaply.  Almost  immediately,  with  two  technicians,  E.  John 
Bell  and  Lyndahl  Hughes,  Cox  went  to  work  making  experimental 
vaccines  against  spotted  fever,  epidemic  typhus,  and  Q  fever.  They 
found  that  even  the  earliest  ones  satisfactorily  protected  guinea  pigs. 
Since  production  required  eggs  instead  of  ticks,  vaccine  manufacture 
would  no  longer  be  tied  to  a  geographical  location  where  ticks  were 
widely  available.  Further,  the  cost  of  production  would  drop  dra- 
matically, so  commercial  firms  could  be  expected  to  take  over  pro- 


Dr.  Cox's  Versatile  Egg 


i8i 


duction  of  the  Cox  vaccine,  as  it  came  to  be  called.  The  cultivation 
of  rickettsiae  in  eggs  also  made  it  unnecessary  to  stock  thousands  of 
laboratory  animals  in  w^hich  strains  of  the  diseases  w^ere  previously 
maintained.  Many  other  lines  of  research  suddenly  became  fruitful, 
including  metabolic  studies  and  the  concentration  of  antigens  for  di- 
agnostic tests  and  for  the  production  of  improved  therapeutic  immune 
sera.  "The  features  that  make  the  yolk  sac  technique  of  particular 
value,"  Cox  himself  noted  in  1941,  v^hen  he  accepted  the  American 
Association  for  the  Advancement  of  Science's  Theobald  Smith  Av^ard, 
"are  its  extreme  simplicity  and  the  ease  w^ith  v^hich  cultures  may  be 
maintained  v^ith  a  minimal  risk  of  contamination."^^ 

At  the  same  time  that  Cox  was  developing  his  yolk  sac  method, 
Hans  Zinsser  and  his  associates  in  the  department  of  bacteriology  and 
immunology  at  Harvard  University  School  of  Medicine  were  devel- 
oping an  alternative  method  to  culture  rickettsiae.  Like  Ida  Bengtson's 
attempts  v^ith  modified  Maitland  media,  the  Harvard  group  sought  to 
utilize  tissue  cultures,  but  they  chose  spleen  tissue  on  agar  slants.  By 
1939  they  reported  some  success  w^ith  the  method  and  described  their 
vaccine  production  technique.^'  Thus  by  the  end  of  the  decade,  three 
new  methods  v^ere  available  in  the  United  States  for  the  culture  of 
rickettsiae:  Bengtson's  modified  Maitland  media  technique.  Cox's  yolk 
sac  method,  and  Zinsser's  agar  slant  approach. 

Over  the  next  two  years.  Cox  compared  the  practicality  of  his 
method  v^ith  Bengtson's,  and  researchers  at  the  Lederle  Laboratories, 
a  division  of  the  American  Cyanamid  Company,  measured  the  im- 
munizing values  and  ease  of  preparation  of  the  Cox  vaccine  against 
the  agar  slant  tissue  culture  vaccine.  With  Bengtson's  method.  Cox 
pointed  out,  it  wsls  difficult  to  produce  a  vaccine  of  consistent  potency. 
Technical  difficulties  w^ith  the  Maitland  method,  moreover,  w^ould 
make  large-scale  production  difficult.  The  Lederle  group  arrived  at  a 
similar  conclusion  about  agar  slant  culture.  In  low  doses,  they  found, 
the  Cox  vaccine  protected  guinea  pigs  better.  "We  have  made  large 
volumes  of  vaccine  by  both  methods  and  are  convinced  that  under  the 
conditions  necessary  to  produce  vaccine  in  large  amounts  the  yolk  sac 
technic  [sic]  is  also  easier  to  carry  out  and  much  less  costly  in  time 
and  materials. "^^ 

By  1940,  Cox's  Rocky  Mountain  spotted  fever  vaccine  was  ready 
to  be  used  experimentally  in  humans.  Ralph  R.  Parker  cheerfully  in- 
formed the  surgeon  general  that  the  vaccine  appeared  safe  and  that 
"likely"  it  w^ould  "soon  replace  the  tick-tissue  product  now  employed." 
After  September  1939,  however,  when  war  broke  out  in  Europe,  the 
peacetime  focus  on  indigenous  spotted  fever  gave  way  to  concern  about 


l82 


Rocky  Mountain  Spotted  Fever 


A  technician  in  the  1940s  is  shown  harvesting  yolk  sacs  from  eggs  infected 
with  rickettsial  organisms.  (Courtesy  of  the  Rocky  Mountain  Laboratories, 
NIAID.) 


the  international  wartime  threat  of  epidemic,  louse-borne  typhus.  Out- 
breaks of  typhus  were  expected  in  Hungary  and  Romania,  where 
thousands  of  Polish  refugees  had  fled  the  German  invasion.  In  order 
to  test  the  efficacy  of  Cox's  experimental  typhus  vaccine,  forty  liters 
were  forwarded  to  five  isolated  Hungarian  villages.  A  portion  of  the 
refugees  received  the  vaccine  while  others  were  left  unvaccinated  as 
controls.  When  Germany  invaded  the  Balkans,  Hungary  was  absorbed 
into  the  Axis  bloc,  and,  unfortunately,  all  records  of  the  test  were 
lost.i^ 

Although  the  threat  of  war  loomed  large  in  1940  and  1941,  the 
United  States  remained  neutral  in  the  conflict.  Public  health  officials 
could  make  only  contingency  plans  for  dealing  with  what  Surgeon 
General  Thomas  Parran  called  the  "national  defense  emergency."^° 
Among  those  plans  was  a  concentrated  effort  to  improve  the  epidemic 
typhus  vaccine  prepared  by  Cox's  technique,  for  any  involvement  in 


Dr.  Cox's  Versatile  Egg 


183 


the  hostilities  would  place  U.S.  military  forces  at  risk  of  contracting 
the  classic  scourge  of  armies.  Military  strategists  who  evaluated  pos- 
sible sites  for  a  second  front  in  Europe  carefully  weighed  the  danger 
of  typhus  in  their  dehberations.  The  disease  certainly  militated  against 
the  Balkans  as  an  invasion  site.  "Typhus  was  accordingly  looked  upon 
as  one  of  the  great  disease  threats  that  must  be  nullified  if  the  Army 
was  going  to  achieve  its  aim  of  reducing  disease  incidence  to  a  point 
at  which  it  would  finally  become  a  minor  casualty  producer,"  wrote 
a  U.S.  Army  physician  in  a  postwar  retrospective  article.  World  War 
I  delousing  techniques  — bathing  and  steam  or  chemical  treatment  of 
clothing— had  proved  at  best  to  be  only  temporary.  The  magnitude  of 
the  perceived  typhus  threat,  therefore,  provided  great  impetus  to  re- 
search on  the  promising  but  unproven  Cox  vaccine. 

At  the  NIH  in  Bethesda,  Maryland,  Norman  H.  Topping,  the  new 
chief  of  the  typhus  unit,  directed  an  intensive  research  program  to  this 
end.  The  son  of  an  obstetrician.  Topping  had  grown  up  in  Los  Angeles, 
where  his  family  moved  after  his  birth  on  12  January  1908  in  Flat 
River,  Missouri. After  taking  his  M.D.  in  1936  from  the  University 
of  Southern  CaUfornia  and  deciding  against  going  into  private  practice, 
the  young  physician  chose  to  pursue  a  career  in  the  U.S.  PubUc  Health 
Service.  An  internship  in  San  Francisco  was  followed  by  duty  rotations 
before  Topping  was  assigned  to  the  NIH  in  July  1937.  He  arrived  just 
before  the  September  class  of  young  officers— the  first  new  group  to 
receive  research  training  since  the  beginning  of  the  Depression.  For  a 
short  period.  Topping  worked  on  dental  research,  but  when  Rolla  E. 
Dyer  invited  him  to  join  the  typhus  unit,  he  enthusiastically  took  up 
the  study  of  spotted  fever  and  Q  fever.  In  1938,  Topping's  interest  in 
combating  these  diseases  became  somewhat  more  than  just  an  intel- 
lectual challenge.  On  30  December  he  was  admitted  to  Walter  Reed 
General  Hospital  "because  of  his  own  diagnosis  of  Rocky  Mountain 
spotted  fever."  Described  by  the  attending  physician  as  "a  dejected 
man  with  a  'hangover'  appearance"  and  a  temperature  of  103.8°  F, 
Topping  suffered  with  spotted  fever  for  nineteen  days  but  eventually 
made  a  complete  recovery.^^ 

Beginning  in  1939,  Topping  and  his  colleagues  in  the  NIH  typhus 
unit  focused  on  evaluating  and  improving  the  Cox  vaccine.  They  be- 
lieved that  Cox's  technique  offered  the  most  cost-effective  method,  but 
in  initial  tests  the  experimental  vaccine  proved  insufficiently  concen- 
trated to  protect  guinea  pigs  against  large  doses  of  virulent  typhus 
rickettsiae.  Because  of  this  setback,  the  typhus  unit  felt  impelled  to 
evaluate  vaccines  made  by  techniques  developed  outside  the  United 
States.  In  1930  a  Polish  investigator,  Rudolf  Weigl,  had  produced  the 


i84 


Rocky  Mountain  Spotted  Fever 


first  of  these  vaccines,  which  was  similar  to  the  Spencer-Parker  tick 
tissue  vaccine  for  spotted  fever.  Weigl  isolated  individual  Hce  under  a 
microscope  and,  with  a  tiny  needle,  inoculated  them  intrarectally  with 
typhus-infected  blood.  Batches  of  these  lice  were  then  fed  for  a  week 
or  more  on  human  volunteers  who  had  recovered  from  typhus.  Finally, 
Weigl  excised  the  infective  gut  tissue  of  each  louse  and  treated  it  with 
phenol.  Tissue  from  fifty  to  one  hundred  lice  was  required  to  immunize 
a  single  individual.  Although  Weigl's  vaccine  was  efficacious,  it  was 
hardly  adaptable  to  large-scale  production. 

Another  approach  to  preparing  a  vaccine  against  the  endemic  form 
of  typhus  transmitted  by  fleas  had  been  pursued  by  Hans  Zinsser's 
long-time  Mexican  collaborator,  M.  Ruiz  Castaneda.  Announced  a 
year  before  Zinsser's  untimely  death  from  leukemia  in  1940,  this  vac- 
cine was  made  from  the  lungs  of  rats  that  had  been  infected  intranasally 
with  murine  typhus  rickettsiae.^^  Ruiz  Castaneda's  method  of  growing 
rickettsiae  was  simple,  but  it  was  suitable  only  for  murine  typhus 
vaccines.  The  rickettsiae  of  epidemic  typhus  did  not  multiply  to  any 
extent  in  rats.  In  1940,  however,  two  French  researchers  prepared  a 
mouse  lung  vaccine  against  epidemic  typhus  fever  that  protected  guinea 
pigs.  Even  this  promising  vaccine,  wrote  Norman  H.  Topping,  had 
"several  disadvantages  when  compared  to  cultivation  of  the  rickettsiae 
in  fertile  hens'  eggs."  In  most  locaHties,  animals  were  more  expensive, 
the  intranasal  inoculation  of  animals  with  viable  rickettsiae  was  an 
extremely  dangerous  procedure,  and  possible  contamination  of  the 
vaccine  with  naturally  occurring  rodent  diseases  could  not  be  elimi- 
nated as  a  hazard. 

Herald  R.  Cox's  method,  even  with  its  limitations,  thus  appeared 
more  promising  than  others  available,  especially  after  a  Canadian 
investigator  developed  a  technique  that  improved  it  significantly.  James 
Craigie,  a  researcher  in  the  Connaught  Laboratories  of  the  University 
of  Toronto  School  of  Hygiene,  employed  ethyl  ether  to  promote  sep- 
aration of  rickettsiae  from  the  tissue  in  which  they  were  cultivated. 
His  method  depended  on  the  fact  that  rickettsiae,  like  a  number  of 
viruses,  such  as  poliomyelitis  and  vaccinia,  and  like  many  pathogenic 
bacteria,  were  repelled  from  the  interface  of  ether-water  mixtures, 
while  insoluble  tissue  or  medium  constituents  were  selectively  attracted 
to  the  interface.  Ethyl  ether  had  the  additional  advantage  of  being 
bactericidal  and  capable  of  rendering  rickettsiae  noninfective  with  great 
rapidity.^^ 

When  the  Japanese  bombed  Pearl  Harbor  on  7  December  1941,  and 
the  United  States  entered  the  war,  bringing  the  vaccine  into  production 
for  military  use  became  imperative.  On  1 1  December,  Dyer  and  Top- 


Dr.  Cox's  Versatile  Egg 


185 


ping,  along  with  officials  of  the  U.S.  Army,  U.S.  Navy,  and  Division 
of  Biologies  Control  at  NIH,  traveled  to  Toronto  to  study  Craigie's 
ether  separation  technique.  Thus  was  launched  an  intensive  research 
effort  to  improve  the  vaccine  by  Cox  in  Montana,  by  the  NIH  typhus 
team  in  Bethesda,  and  by  Harry  Plotz's  group  at  the  Division  of  Virus 
and  Rickettsial  Diseases  at  the  U.S.  Army  Medical  School  in  Wash- 
ington, D.C. 

Cox  had  little  luck,  but  the  Washington  and  Bethesda  groups  made 
progress.  Ida  A.  Bengtson  found  a  way  to  increase  the  yield  of  rick- 
ettsiae  from  yolk  sacs,  and,  with  Topping,  discovered  that  alum  pre- 
cipitation increased  the  vaccine's  ability  to  produce  complement  fixing 
antibodies.  Topping  and  M.  J.  Shear  discovered  that  a  soluble  antigen, 
which  had  previously  been  discarded,  could  be  added  to  the  vaccine 
to  enhance  protective  power.  Plotz  and  his  colleagues  at  the  U.S.  Army 
Medical  School  also  identified  this  antigen,  almost  simultaneously. 
Bengtson,  Topping,  and  Richard  G.  Henderson  demonstrated  a  toxin 
produced  by  the  epidemic  typhus  organism  in  yolk  sac  cultures,  an 
observation  that  permitted  development  of  a  mouse  neutralization  test 
for  the  vaccine. 

As  the  United  States  mobilized  for  war,  the  NIH  typhus  unit  was 
pressed  to  define  standard  vaccine  production  methods,  even  though 
research  was  incomplete  and  the  early  experiments  revealed  that  several 
approaches  produced  equally  effective  protection.  In  August  1942, 
Topping  outlined  the  best  method  then  known  for  producing  epidemic 
typhus  vaccine  in  a  directive  prepared  for  restricted  circulation.  He 
cautioned  that  further  refinements  might  be  forthcoming.  With  regard 
to  the  Craigie  ether  extraction  method.  Topping  observed  that  it  had 
"already  been  modified  several  times"  and  that  as  work  progressed, 
further  modifications  would  probably  be  necessary.^^ 

The  tight  control  exercised  over  this  and  all  other  scientific  publi- 
cations relating  to  typhus  during  the  war  clearly  reflected  the  strategic 
importance  of  the  research.  At  the  NIH  investigators  were  assigned 
publication  dates  in  the  Public  Health  Reports  in  order  to  provide 
documentation  of  their  research  for  later  peacetime  career  consider- 
ations. Virtually  no  paper  on  matters  relating  to  military  medicine  was 
published  openly;  most  were  circulated  in  mimeographed  form  to 
Allied  researchers  working  in  the  same  field. 

Additional  human  trials  of  the  improved  vaccine  were  needed,  and 
Topping  worked  with  Rolla  E.  Dyer  to  locate  an  area  in  which  typhus 
epidemics  occurred  frequently  but  which  was  less  volatile  than  war- 
torn  Hungary.  In  August  194 1  they  arranged  through  the  Pan  American 
Sanitary  Bureau,  headed  by  former  Surgeon  General  Hugh  S.  Cum- 


i86 


Rocky  Mountain  Spotted  Fever 


ming,  to  test  the  vaccine  on  Indian  miners  in  isolated  villages  in  Bolivia. 
Unfortunately,  the  follow-up  by  an  official  of  the  Bolivian  health  de- 
partment w^as  inconclusive. Another  test  of  the  vaccine  was  under- 
taken by  Rockefeller  Foundation  researchers  working  in  Spain,  where 
an  epidemic  had  struck  ten  thousand  people.  John  H.  Janney  and  John 
C.  Snyder  of  the  foundation  hoped  for  a  controlled  study  in  Spanish 
prisons,  but  turnover  in  the  prison  population  thwarted  their  plans. 
When  Pearl  Harbor  was  bombed,  moreover,  they  were  forced  to  in- 
terrupt their  work  to  return  home.  On  the  basis  of  hmited  evidence, 
Spanish  observers  believed  that  the  vaccine  did  help  to  control  the 
spread  of  the  disease.  Further  evidence  was  gained  when  Snyder  and 
four  laboratory  assistants,  who  had  been  vaccinated  with  the  Cox 
material,  contracted  typhus  in  the  laboratory  and  suffered  exception- 
ally mild  cases. 

With  suggestive  but  not  conclusive  proof  of  efficacy,  epidemic  typhus 
vaccine  prepared  by  Cox's  method  with  various  modifications  went 
into  wartime  production.  Spotted  fever  vaccine  also  continued  to  be 
manufactured  with  rickettsiae  propagated  in  yolk  sacs,  and  it  benefited 
from  the  improved  methods.  Because  Cox's  spotted  fever  vaccine  was 
so  much  simpler  and  cheaper  to  produce— and  apparently  at  least  as 
effective  as  the  tick  tissue  product— the  Rocky  Mountain  Laboratory 
ceased  production  of  the  Spencer-Parker  vaccine  in  1942  as  an  economy 
measure.  Later,  small  lots  of  tick  tissue  vaccine  were  again  produced 
because  of  reports  that  some  recipients  were  allergic  to  egg  proteins 
in  the  Cox  vaccines.  The  number  of  people  at  risk  of  contracting  spotted 
fever  was  small,  however,  when  compared  to  the  threat  of  typhus  in 
military  and  civihan  populations.  Research  on  Rocky  Mountain  spot- 
ted fever  thus  "drifted  to  the  side  lines  of  activity"  at  the  RML.  Within 
the  year,  representatives  of  commercial  firms  were  visiting  the  labo- 
ratory, seeking  to  learn  how  to  produce  typhus  vaccine,  and  two 
national  magazines  featured  the  work  in  reviews  of  wartime  diseases. 
Cox  himself  left  Montana  at  the  end  of  1942  to  accept  the  position 
of  associate  director,  later  director,  of  viral  research  at  Lederle  Lab- 
oratories.^^ 

During  the  war,  the  Rocky  Mountain  Laboratory,  established  in  the 
remote  Bitterroot  Valley  to  produce  a  vaccine  against  what  was  con- 
sidered to  be  a  local  disease,  literally  became  a  national  vaccine  factory. 
In  addition  to  typhus  and  spotted  fever  vaccines,  the  facility  also 
produced  yellow  fever  vaccine  for  the  military.^^  The  laboratory's  stra- 
tegic importance  was  reflected  in  the  extraordinary  security  mounted 
to  protect  it.  Immediately  after  the  Japanese  attack  on  Pearl  Harbor, 
two  night  watchmen  were  ordered  deputized  and  additional  ones  were 


Dr.  Cox's  Versatile  Egg 


187 


By  the  1940s,  the  Rocky  Mountain  Laboratory  had  grown  through  the 
addition  of  several  new  wings  and  buildings.  During  World  War  II,  the 
laboratory^  produced  vaccines  against  typhus,  yellow  fever,  and  Rocky 
Mountain  spotted  fever.  (Courtesy  of  the  Rocky  Mountain  Laboratories, 
NIAID.) 


armed.  Beginning  on  i  January  1942,  armed  guards  were  placed  on 
duty  at  all  times. 

Rocky  Mountain  spotted  fever  proved  to  be  a  minimal  problem  for 
the  military  during  the  war.  Only  eighty-one  cases  occurred  among 
U.S.  Army  personnel,  and  more  than  half  of  these  were  recorded  during 
1943,  when  large  numbers  of  troops  were  in  training  camps  around 
the  United  States.  Thirteen  deaths  among  these  cases  produced  a  mor- 
tality rate  of  16.05  percent— lower  than  the  18.89  percent  national 
average  recorded  between  193 1  and  1946.  Early  in  the  war  the  army 
adopted  a  policy  of  limited  vaccination,  targeting  only  those  personnel 
such  as  patrols  and  guards  who  routinely  worked  in  tick-infested, 
endemic  areas.  In  1942  the  RML  provided  enough  vaccine  to  vaccinate 
twenty  thousand  military  personnel.  Because  this  amount  appeared  to 
be  excessive,  the  quantity  was  reduced.  Only  ten  thousand  people  were 
vaccinated  in  1943  and  just  thirty-five  hundred  in  1944.  In  1945, 
however,  the  U.S.  Army  required  vaccine  for  sixteen  thousand  people 
because  of  the  large  number  of  prisoners  of  war  housed  in  endemic 
areas. 


i88 


Rocky  Mountain  Spotted  Fever 


Casualties  from  spotted  fever  did  not  occur  among  military  personnel 
alone,  of  course.  One  wartime  domestic  infection  was  especially  no- 
table because  it  contributed  to  expanded  worker's  compensation  rights. 
In  1942  a  Utah  man  engaged  in  outdoor  work  was  bitten  on  his  hand 
by  "something,"  which  he  brushed  off.  A  week  later  he  was  hospitahzed 
with  a  severe  spotted  fever  infection,  and  he  died  shortly  thereafter. 
Alleging  that  her  husband's  death  was  due  to  a  tick  bite  suffered  in 
the  course  of  his  work,  the  widow  sued  and  was  awarded  compen- 
sation. His  employer  appealed  this  decision  to  the  Utah  Supreme  Court, 
arguing  that  ticks  almost  never  bit  humans  on  the  hand,  hence  the 
infection  was  more  likely  contracted  during  the  victim's  leisure  time. 
The  court,  however,  observed  that  the  victim  worked  in  or  near  tick- 
infested  brush  areas  and  that  the  sequence  of  events  was  consistent 
with  the  pattern  of  fulminating  spotted  fever.  Because  of  this  it  could 
be  inferred  "that  the  deceased  picked  up  the  tick  in  the  course  of  his 
employment,"  hence  the  compensation  award  to  the  widow  was  sus- 
tained.^^ 

The  nation's  attention  and  principal  rickettsial  research  effort,  how- 
ever, was  focused  not  on  spotted  fever  but  rather  against  epidemic 
typhus,  the  greatest  direct  threat  to  Allied  troops.  Without  attempting 
to  do  justice  to  the  story  of  typhus  in  World  War  II— a  subject  that 
deserves  its  own  fuller  treatment— a  brief  survey  of  the  administrative 
machinery  and  major  results  of  typhus  control  efforts  is  in  order.  Most 
of  the  leading  postwar  investigators  in  spotted  fever  and  other  rick- 
ettsial diseases  established  contacts  and  gained  experience  in  the  cru- 
cible of  war,  and  the  focus  of  their  efforts  was  this  close  relative  of 
Rocky  Mountain  spotted  fever.  Many  preventive  and  therapeutic  mea- 
sures developed  for  typhus,  moreover,  were  adapted  for  application 
against  spotted  fever. 

The  threat  of  classic,  epidemic  typhus  to  U.S.  military  forces  was 
first  addressed  in  1942  as  the  invasion  of  North  Africa  was  being 
planned.  There  were  reports  of  typhus  cases  among  the  populations 
of  Algeria  and  Morocco  and  of  increasing  numbers  of  cases  in  Egypt. 
Because  of  this,  leaders  of  the  U.S.  Army,  U.S.  Navy,  and  U.S.  Public 
Health  Service  promoted  the  formation  of  a  special  commission  to 
coordinate  efforts  for  combatting  it.  On  Christmas  eve  1942,  President 
Franklin  D.  Roosevelt  signed  the  extraordinary  Executive  Order  9285, 
establishing  the  United  States  of  America  Typhus  Commission.  Sep- 
arate from  other  committees  created  to  deal  with  the  multiple  medical 
and  scientific  problems  of  the  war,  the  Typhus  Commission  was 
granted  wide-ranging  powers  to  protect  U.S.  troops  against  typhus 


Dr.  Cox's  Versatile  Egg 


189 


wherever  it  occurred  or  even,  in  the  words  of  the  order,  where  it  "may 
become  a  threat."  In  addition,  it  was  empowered  to  prevent  the  in- 
troduction of  typhus  into  the  United  States.  Composed  of  represen- 
tatives of  the  U.S.  Army,  U.S.  Navy,  and  U.S.  PubHc  Heahh  Service, 
the  commission  was  originally  headed  by  Charles  S.  Stephenson,  chief 
of  the  Preventive  Medicine  Service  in  the  Bureau  of  Medicine  and 
Surgery  of  the  U.S.  Navy,  who  reported  directly  to  the  secretary  of 
war.  Stephenson  resigned  in  February  1943  because  of  illness,  and  in 
August  1943  his  successor,  Leon  A.  Fox  of  the  U.S.  Army  Medical 
Corps  requested  transfer  to  a  position  as  field  director.  Stanhope  Bayne- 
Jones,  also  of  the  U.S.  Army  Medical  Corps,  then  assumed  the  direc- 
torship, which  he  held  until  1946,  when  the  commission  was  dis- 
solved.^^ 

Because  epidemic,  louse-borne  typhus  occurred  rarely  in  the  United 
States,  most  miHtary  physicians  had  never  seen  a  case  of  the  disease. 
In  February  1943  the  U.S.  Army  Surgeon  General's  Office  sent  a  group 
of  medical  officers  to  Guatemala  to  observe  an  outbreak  of  suspected 
epidemic  typhus.  Since  murine  typhus  was  known  to  be  present  in 
Guatemala,  and  since  it  could  be  spread  epidemically  by  lice  as  well 
as  by  fleas,  it  was  originally  unclear  which  type  of  typhus  had  stricken 
the  area.  Eugene  P.  Campbell  and  Robert  Vought,  physicians  working 
for  the  Institute  of  Inter- American  Affairs,  another  extraordinary  war- 
time government  organization,  believed  from  epidemiological  and  clin- 
ical information  that  this  was,  indeed,  classic,  louse-borne  typhus. 
Blood  samples  from  several  villages  were  sent  to  the  U.S.  Army  Medical 
School,  where  both  the  Weil-Felix  test  and  the  newly  developed  com- 
plement fixation  test  confirmed  their  clinical  diagnosis.  "With  war 
coming  on,"  Campbell  observed,  "the  lack  of  clarity  and  reHability  in 
distinguishing  endemic— mild,  or  flea-transmitted— typhus  from  the 
serious,  epidemic,  louse-borne  infection  was  a  great  concern  to  us  in 
the  field."^^  With  such  abbreviated  experiences,  U.S.  military  physi- 
cians prepared  to  deal  with  expected  epidemics,  for  much  military 
action  was  anticipated  in  known  typhus  foci. 

By  the  time  U.S.  troops  went  into  North  Africa,  all  had  received  the 
Cox  vaccine  against  typhus.  During  the  course  of  the  war,  the  U.S.A. 
Typhus  Commission  distributed  vaccine  to  some  30  million  people. 
Much  was  funneled  through  British  organizations  and  through  the 
health  division  of  the  United  Nations  Relief  and  Rehabilitation  Ad- 
ministration, which  combated  epidemic  diseases  among  civilians. 
Although  typhus  did  attack  civilians  in  war-torn  areas,  in  prisons,  and 
in  the  concentration  camps  in  German-occupied  areas,  it  proved  to  be 


190 


Rocky  Mountain  Spotted  Fever 


of  little  consequence  to  the  U.S.  military  effort.  Between  1942  and 
1945  there  were  only  104  cases  of  epidemic  typhus  among  U.S.  military 
personnel  and  no  deaths. 

Although  this  record  might  imply  that  the  Cox  vaccine  had  succeeded 
admirably,  British  and  U.S.  studies  were  inconclusive  about  whether 
the  vaccine  actually  reduced  incidence  of  naturally  acquired  typhus. 
On  the  other  hand,  all  observers  agreed  that  it  was  highly  effective  in 
reducing  the  case  fatality  rate."^^  A  principal  reason  that  typhus  never 
seriously  challenged  vaccinated  U.S.  troops  was  the  development  of 
an  effective  insecticide,  the  widespread  use  of  which  stopped  nascent 
epidemics  among  civiHan  populations  before  they  began.  This  chemical 
was  dichloro-diphenyl-trichloroethane,  more  commonly  called  DDT. 

First  produced  in  1874,  DDT  was  not  discovered  to  have  insect- 
kiUing  powers  until  1939,  after  which  a  wave  of  research  was  con- 
ducted on  its  potential  as  a  means  to  kill  disease-carrying  lice  and 
mosquitoes.  Major  federal  agencies  involved  in  this  work  included  the 
Bureaus  of  Entomology  and  Plant  Quarantine  of  the  U.S.  Departm.ent 
of  Agriculture,  the  Division  of  Pharmacology  of  the  U.S.  Food  and 
Drug  Administration,  and  the  National  Institute  of  Health.  The  In- 
ternational Health  Division  of  the  Rockefeller  Foundation  also  con- 
tributed to  the  effort,  and  all  research  was  coordinated  by  the  National 
Research  Council  and  the  Committee  on  Medical  Research  of  the  Office 
of  Scientific  Research  and  Development.  Two  earHer  powders  lethal 
to  hce— MYL  in  the  United  States  and  AL-63  in  England— had  been 
used  with  some  success,  but  neither  proved  to  be  as  effective  as  DDT. 
When  short-term  preliminary  tests,  conducted  primarily  in  an  Orlando, 
Florida,  laboratory  and  at  U.S.  Department  of  Agriculture  laboratories 
in  Beltsville,  Maryland,  indicated  that  DDT  was  nontoxic  for  humans 
or  animals,  the  chemical  was  ruled  safe— despite  warnings  from  the 
Audubon  Society  — and  adopted  by  the  U.S.  Army  in  1943  as  the 
standard  agent  to  be  used  against  lice."^^ 

Before  the  advent  of  DDT,  the  appHcation  of  insecticide  to  indivi- 
duals was  a  cumbersome,  awkward,  and  time-consuming  process.  Peo- 
ple had  to  remove  their  clothes,  which  were  then  dusted  by  hand,  with 
great  care  taken  to  apply  the  insecticide  to  the  seams  where  lice  often 
hid.  The  Rockefeller  Foundation's  typhus  team,  however,  found  that 
the  new  powder  could  be  applied  with  a  "blowing  machine"  to  puff 
it  under  clothes  without  their  wearers  having  to  remove  them.  Not 
only  was  the  method  faster,  but  it  was  also  accepted  by  even  the  most 
modest  civilians.  A  curious  side  effect  of  the  new  chemical  was  its  sale 
on  the  black  market  in  many  countries  because  it  was  thought  to  be 
an  opiate.  "These  people  could  sleep  after  they  got  deloused,"  remarked 


Dr.  Cox's  Versatile  Egg 


191 


Stanhope  Bayne-Jones.  "They  thought  that  this  was  the  best  sleep 
producing  drug  that  they  had  ever  come  across. '"^^ 

Three  months  after  AlHed  forces  landed  in  Italy  in  September  1943, 
an  epidemic  of  typhus  in  Naples  provided  the  first  true  test  of  DDT's 
effectiveness.  U.S.  Army  medical  officers  cooperated  with  officials  of 
the  U.S.A.  Typhus  Commission  and  with  representatives  of  the  Rock- 
efeller Foundation.  They  identified  and  isolated  cases  and  dusted  as 
many  members  of  the  civilian  population  as  possible  with  DDT.  A 
Rockefeller  Foundation  report  on  the  dusting  operation  observed: 
"This  system  of  rapid  dusting  without  disrobing  enabled  the  mass 
dusters  to  care  for  as  many  as  66,000  patrons  a  day.  More  than 
1,300,000  were  treated  in  January  [1944]  alone  — and  Naples  has  a 
population  of  less  than  1,000,000,  which  shows  that  some  people 
came  for  more  than  one  treatment.  .  .  .  The  epidemic  in  Naples  which 
might  have  taken  thousands  of  lives  collapsed  with  astonishing  rapid- 
ity."^ 

The  very  success  of  DDT  in  controlling  epidemics  of  typhus  fore- 
stalled a  large-scale  evaluation  of  the  Cox  vaccine's  preventive  powers 
under  wartime  conditions.  In  contrast,  the  yolk  sac  technique  for 
cultivating  rickettsiae  clearly  proved  itself  as  a  means  to  produce  the 
concentrated  antigens  necessary  for  developing  a  more  sensitive  di- 
agnostic tool  for  typhus  and  for  Rocky  Mountain  spotted  fever.  Con- 
structing a  useful  laboratory  test  for  any  infectious  disease  depended 
on  the  availability  of  strong  antigens  that  would  react  with  antibodies 
in  a  patient's  serum  to  cause  clumping  or  some  other  visible  reaction 
in  a  test  tube.  The  necessary  antigens  were  obtained  by  growing  large 
quantities  of  a  pathogenic  organism.  Before  Cox  discovered  that  rick- 
ettsiae would  multiply  luxuriantly  in  yolk  sacs  of  the  developing  chick 
embryo,  researchers  were  hampered  by  the  limitations  of  cultivating 
them  in  their  arthropod  vectors.  Laboratory  diagnosis  was  thus  re- 
stricted to  the  guinea  pig  infection  test  first  pioneered  by  Howard 
Taylor  Ricketts  or  to  the  Weil-Felix  test  developed  in  19 16. 

Before  the  mid  1920s,  the  need  for  more  sensitive  tests  had  not 
appeared  acute,  because  the  geographical  location  of  typhus-like  symp- 
toms seemed  to  define  their  nature.  Spotted  fever  was  believed  to  be 
confined  to  the  northwestern  states.  Typhus,  initially  viewed  exclu- 
sively as  a  louse-borne  disease,  was  thought  to  be  absent  from  the 
United  States,  except  for  occasional  outbreaks  around  New  York, 
which  were  attributed  to  importation  of  the  disease  from  Europe  and 
thought  to  be  self-hmiting.  Brill's  disease,  viewed  as  a  pecuHar,  httle- 
understood  manifestation  of  typhus  in  New  York  City,  conformed  to 
the  larger  pattern.  In  1926,  however,  when  Kenneth  F.  Maxcy  described 


192 


Rocky  Mountain  Spotted  Fever 


the  endemic  form  of  typhus  existing  in  the  eastern  United  States,  this 
geographical  scheme  was  disrupted.  A  second  type  of  typhus  required 
some  means  to  differentiate  it  from  the  classic  epidemic  form.  In  193 1, 
when  the  NIH  typhus  unit  reported  the  existence  of  spotted  fever  in 
east-coast  states,  further  impetus  was  given  to  the  search  for  better 
diagnostic  techniques  for  the  rickettsial  diseases. 

Throughout  the  1930s,  the  Weil-Felix  reaction  remained  the  only 
serological  test  available  to  confirm  chnical  observations.  Initially  de- 
veloped as  a  means  to  detect  epidemic  typhus,  the  test  was  examined 
in  1923  by  F.  L.  Kelly  for  its  possible  use  as  a  diagnostic  tool  for 
spotted  fever.  Kelly's  research  indicated  that  no  reaction  was  obtained 
with  the  sera  of  spotted  fever  patients.  In  1928,  however,  LeRoy  Kerlee 
and  Roscoe  R.  Spencer  reported  in  a  paper  published  shortly  after 
Kerlee  died  that  the  Weil-Felix  test  was  indeed  useful  in  spotted  fever. 
Noting  that  Kelly  had  made  only  a  few  titrations  and  studied  only 
nine  cases,  early  in  the  disease,  Kerlee  and  Spencer  used  the  OX- 19 
strain  of  B.  proteus  to  test  sera  taken  at  intervals  from  seven  days  to 
one  year  after  disease  onset.  Their  research  showed  that  agglutination 
became  more  complete  as  the  diseases  progressed  and  that  agglutinins 
persisted  longer  in  patients  suffering  from  spotted  fever  than  in  those 
with  typhus."^^ 

Two  years  later,  Spencer  and  Maxcy,  who  had  used  the  Weil-Felix 
test  extensively  for  diagnosis  in  typhus  cases,  repeated  Kelly's  earlier 
experiments  with  a  larger  number  of  spotted  fever  and  endemic  typhus 
cases,  using  sera  taken  late  in  the  disease.  They  found  that  the  agglu- 
tination reaction  was  different  in  spotted  fever  and  typhus.  Spotted 
fever  produced  agglutinins  of  broader  affinities  and  greater  variability 
than  those  produced  by  typhus.  Although  the  two  diseases  were  closely 
related  antigenically,  typhus  and  spotted  fever  were  immunologically 
distinct.  Neither  disease  afforded  protection  to  recovered  animals 
against  inoculation  by  the  other."^^ 

Since  the  serum  of  typhus  patients  agglutinated  the  OX- 19  strain 
of  JB.  proteus  at  high  titers  and  that  of  spotted  fever  patients  at  low 
titers,  the  Weil-Felix  test  provided  a  rough  mechanism  to  differentiate 
between  the  two  diseases.  As  the  only  laboratory  technique  available, 
by  the  early  1930s  it  has  been  widely  adopted  in  the  United  States  to 
confirm  clinical  diagnoses.  It  was  of  no  value  early  in  the  disease,  of 
course,  because  the  reaction  depended  on  the  increase  of  antibodies 
as  the  body  fought  off  the  invading  organisms.  It  was  also  useless  if 
the  patient  died  before  sufficient  antibodies  had  been  produced."^^  An- 
other major  drawback  was  its  ambiguity  in  mild  or  atypical  rickettsial 
infections,  those  cases  most  difficult  to  diagnose  clinically  as  well. 


Dr.  Cox's  Versatile  Egg 


193 


Curiously,  although  guinea  pigs  were  the  principal  animal  model 
used  in  rickettsial  disease  research,  their  sera  did  not  agglutinate  in 
the  Weil-Felix  test."^^  Other  signs  of  infection  in  these  animals  had 
therefore  been  studied  for  their  uniqueness  in  particular  diseases.  Until 
the  mid  1920s,  sweUing  of  the  scrotum  in  male  guinea  pigs  had  been 
considered  diagnostic  for  infection  with  spotted  fever,  and  lesions 
formed  in  the  brains  of  guinea  pigs  indicated  infection  with  epidemic 
typhus.  After  the  identification  of  murine  typhus  in  1926,  however, 
this  simple  scheme  no  longer  sufficed.  Murine  typhus  had  also  been 
shown  to  cause  scrotal  swelling  in  guinea  pigs,  and  in  1933,  Lucius 
F.  Badger  of  the  NIH  typhus  unit  demonstrated  that  brain  lesions  in 
this  laboratory  animal  were  not  limited  to  typhus  infections  but  also 
occurred  in  Rocky  Mountain  spotted  fever.  To  complicate  the  picture 
further.  Badger  reported  that  other  infectious  agents  could  produce 
similar  signs  as  well.  "The  identification  in  the  laboratory  of  an  un- 
known strain  of  virus  as  one  of  endemic  typhus  or  as  one  of  spotted 
fever,"  he  told  a  meeting  of  the  American  Society  of  Tropical  Medicine, 
finally  depended  on  the  production  of  definite  and  complete  cross- 
immunity  with  a  known  strain  of  the  virus  suspected.^° 

During  the  1930s,  Henry  Pinkerton  and  George  M.  Haas  in  the 
Department  of  Pathology  at  Harvard  University  Medical  School  con- 
tributed one  new  tool  to  assist  laboratory  diagnosis  of  rickettsial  dis- 
eases. Beginning  with  S.  Burt  Wolbach's  observation  that  spotted  fever 
rickettsiae  were  found  in  the  nuclei  of  tick  tissues,  Pinkerton  and  Haas 
reported  from  their  own  studies  that  typhus  rickettsiae  multiplied  in 
the  cytoplasm  of  the  cells  but  never  invaded  the  nuclei.  Spotted  fever 
rickettsiae,  regardless  of  how  atypically  the  disease  was  manifest,  grew 
sparsely  in  the  cytoplasm  but  formed  compact  spherical  colonies  in 
the  nuclei  of  infected  cells.  The  Pinkerton-Haas  criteria  proved  useful 
for  laboratory  studies  and  at  autopsies  of  typhus  or  spotted  fever 
victims.  They  were,  of  course,  not  appHcable  in  clinical  diagnosis. 

By  the  early  1940s,  Herald  R.  Cox's  yolk  sac  cultivation  method 
provided  a  means  to  produce  the  concentrated  antigens  necessary  for 
developing  a  new  test  based  on  the  phenomenon  known  as  complement 
fixation.  It  had  first  been  described  in  1901,  when  Jules  Border,  a 
Belgian  scientist,  had  observed  that  an  ingredient  in  the  blood,  which 
he  called  "alexine"  but  is  now  known  as  complement,  was  used  up 
or  fixed  to  cells  in  antigen-antibody  reactions. In  191 1,  Benjamin  F. 
Davis  and  William  F.  Petersen,  associates  of  Howard  Taylor  Ricketts, 
studied  the  complement  fixing  capabiHty  of  spotted  fever  serum.  They 
used  tick  eggs  as  well  as  the  serum  and  macerated  organs  of  infected 
guinea  pigs  as  sources  of  antigens,  but  their  results  were  inconclusive.^^ 


194 


Rocky  Mountain  Spotted  Fever 


Over  the  next  two  decades,  European  researchers  used  alcohohc  ex- 
tracts of  organs  from  fatal  cases  of  epidemic  typhus  as  antigens  to 
study  complement  fixation  in  that  disease,  but  again,  the  results  were 
unsatisfactory/"^  In  1936  M.  Ruiz  Castaneda  first  reported  positive 
complement  fixation  for  typhus  fever  serum  mixed  with  suspensions 
of  endemic  rickettsiae  obtained  from  the  peritoneal  washings  of  in- 
fected x-rayed  rats/^ 

With  the  advent  of  Cox's  easy  method  of  growing  rickettsiae,  a 
sensitive  complement  fixation  test  was  soon  developed. At  the  NIH, 
Ida  A.  Bengtson  and  Norman  H.  Topping  developed  the  test  and 
evaluated  its  usefulness  for  differentiating  rickettsial  diseases  at  the 
same  time  that  they  were  attempting  to  improve  the  Cox  vaccine.  "The 
question  of  differentiation  is  of  special  importance,"  they  noted  in  a 
1942  paper,  "in  those  sections  of  the  country  where  both  endemic 
typhus  and  Rocky  Mountain  spotted  fever  occur,  as  in  the  eastern  and 
southeastern  sections  of  the  country."  Their  studies  showed  that  the 
complement  fixation  test  was  superior  to  the  Weil-Felix  test  according 
to  four  key  criteria.  First,  the  complement  fixation  test  furnished  ev- 
idence of  rickettsial  infection  earlier  than  the  Weil-Felix  test  in  23.9 
percent  of  human  sera  tested.  Second,  it  was  superior  because  the 
complement  fixation  reaction  persisted  longer  than  did  the  Weil-Felix 
reaction.  Third,  low  titers  were  significant  in  the  complement  fixation 
procedure.  Finally,  spotted  fever  sera  tested  negative  nearly  all  the  time 
against  typhus  antigens  in  the  complement  fixation  test,  while  they 
often  gave  a  false  positive  Weil-Felix  reading.^^ 

Harry  Plotz,  Kenneth  Wertman,  and  their  collaborators  at  the  Di- 
vision of  Virus  and  Rickettsial  Diseases  of  the  U.S.  Army  Medical 
School  in  Washington,  D.C.,  confirmed  the  NIH  group's  findings,  using 
rickettsial  antigens  made  by  the  agar  slant  method.  Sera  from  two 
patients  whose  symptoms  were  confusing  tested  clearly  positive  for 
spotted  fever  and  clearly  negative  for  typhus.  Further  studies  comparing 
the  complement  fixation  test  to  the  standard  method  of  observing 
guinea  pig  reactions  also  produced  evidence  of  the  test's  superiority. 
"Irrespective  as  to  whether  the  guinea  pig  develops  evidence  of  disease 
as  expressed  by  a  febrile  reaction  or  scrotal  swelling,  or  an  inapparent 
disease  without  these  reactions,"  they  wrote  in  a  1946  paper,  "specific 
complement  fixing  antibodies  develop  in  early  convalescence.  The  use 
of  the  complement  fixation  reaction,  likewise,  permits  the  detection 
of  those  animals  that  represent  missed  infections  or  those  that  develop 
fever  from  nonspecific  causes.  The  use  of  the  complement  fixation 
method  for  strain  identification  is  specific,  rapid  and  inexpensive."^^ 

By  the  end  of  the  decade,  the  complement  fixation  test  had  joined. 


Dr.  Cox's  Versatile  Egg 


195 


if  nor  supplanted,  the  Weil-Felix  test  as  a  major  diagnostic  tool  in 
rickettsial  disease  studies.  Unfortunately,  reagents  for  both  tests  were 
available  only  from  a  handful  of  laboratories,  principally  those  of  the 
NIH,  the  RML,  and  the  Division  of  Viral  and  Rickettsial  Diseases  of 
the  U.S.  Army  Medical  School.  Joseph  E.  Smadel,  who  was  on  the 
staff  of  the  last-named  institution,  observed  in  1948  that,  even  with 
the  new  tests,  it  still  took  ten  days  to  three  weeks  to  identif)^  rickettsia 
and  that  such  work  required  the  maintenance  of  a  "museum  of  in- 
fectious agents"  as  well  as  "stocks  of  known  antigens,  antiserums  and 
immune  animals. "^'^  Physicians  or  pubhc  health  workers  mailed  sam- 
ples of  blood  to  the  laboratories  and  waited  the  requisite  time  for  the 
results. 

Furthermore,  scientific  efficiency  could  be  thwarted  by  nature  or  by 
human  error  at  any  link  in  the  chain  from  patient  to  laboratory.  The 
harsh  Montana  winter,  for  instance,  occasionally  interfered  with  anal- 
yses of  blood  samples  sent  to  the  RML.  "The  post  office  sometimes 
left  mail  sacks  out  on  the  platforms  in  minus  thirty  degree  weather," 
recalled  David  B.  Lackman,  former  chief  serologist  at  the  RML.  "Blood 
specimens  in  the  sacks  froze  at  that  temperature,"  producing  an  un- 
usable "syrupy  mess."  Physicians  were  encouraged  to  centrifuge  blood 
specimens  to  remove  the  solid  cells  before  mailing,  he  also  noted,  but 
many  lacked  the  equipment  or  expertise  to  prepare  the  specimens  in 
this  manner.  By  the  1950s,  however,  commercial  firms  were  manu- 
facturing rickettsial  antigens,  which  facilitated  the  establishment  of 
additional  state  or  regional  diagnostic  laboratories. ^° 

The  development  of  the  complement  fixation  test,  coupled  with 
decades  of  experience  with  rickettsial  diseases,  made  short  work  of 
identifvang  a  completely  new  rickettsial  disease  that  appeared  in  Feb- 
ruarv'  1946.  This  malady  was  first  described  as  a  separate  clinical  entity 
among  residents  of  an  apartment  complex  in  Kew  Gardens,  New  York. 
It  was  named  rickettsialpox  to  indicate  that  it  w^as  caused  by  a  rick- 
ettsial organism  and  that  it  had  initially  been  misdiagnosed  as  mild 
chickenpox.  Charles  Pomeranz,  a  local  exterminator  and  amateur  en- 
tomologist, alerted  New  York  health  authorities  to  the  possibility  of 
some  sort  of  arthropod-borne  disease  after  he  found  mite-infested  mice 
m  the  apartment-complex  basement.  When  New  York  investigators 
called  on  the  U.S.  Pubhc  Health  Service  for  assistance,  Robert  J.  Hueb- 
ner  and  his  colleagues  in  the  Division  of  Infectious  Diseases  at  the  NIH 
and  William  L.  Jellison,  entomologist  from  the  RML,  joined  in  the 
collaborative  effort.  They  isolated,  described,  and  classified  the  etio- 
logic  agent  as  a  hitherto  unknown  rickettsia  of  the  spotted  fever  group. 
Because  the  organism  was  found  to  inhabit  the  mite  Allodermanyssus 


Rocky  Mountain  Spotted  Fever 


sanguineus,  a  parasite  of  the  house  mouse,  they  named  it  Rickettsia 
akari,  akari  meaning  "mite."  Epidemiological  research  determined  that 
the  disease  was  contracted  wherever  mites  had  access  to  human  living 
areas.  In  the  case  of  the  original  apartment  complex,  the  mites  climbed 
up  a  central  incinerator  chute  and  infested  the  carpeting  in  apartments, 
thus  rendering  young  children  especially  susceptible.  In  sharp  contrast 
to  the  decades  it  took  to  understand  spotted  fever  and  the  centuries 
during  which  epidemic  typhus  remained  a  mystery,  the  complete  pic- 
ture of  rickettsialpox  was  elucidated  within  eight  months. 

Shortly  before  this  triumph  of  laboratory  investigation,  however, 
another  mysterious  disease  had  eluded  clarification.  In  1942  and  1943 
there  were  "mass  outbreaks  of  an  apparently  new  clinical  syndrome" 
at  Fort  Bullis  in  Texas  that  came  to  be  called  Bullis  fever.  It  resembled 
a  rickettsial  disease,  especially  Q  fever,  and  it  was  linked  to  a  tick 
vector,  but  no  immunological  relationship  between  it  and  any  known 
rickettsiosis  could  be  conclusively  demonstrated.  Since  no  further  cases 
occurred,  investigation  was  halted,  and,  to  the  present,  Bullis  fever 
remains  an  unexplained  mystery. 

Herald  R.  Cox's  spectacularly  successful  method  of  growing  rick- 
ettsiae  in  yolk  sacs  had  been  discovered  in  the  search  for  a  better 
vaccine  against  Rocky  Mountain  spotted  fever.  Two  of  its  most  im- 
portant consequences  were  the  epidemic  typhus  vaccine  that  protected 
U.S.  troops  during  World  War  II  and  the  development  of  the  comple- 
ment fixation  test.  Although  it  was  clearly  an  advance  over  the  culture 
of  rickettsiae  in  ticks  and  in  lice.  Cox's  technique  was  not  without  its 
Hmitations.  Yolk  sac  vaccines  did  not  provide  complete  protection 
against  contracting  rickettsial  diseases,  although,  fike  the  Spencer- 
Parker  vaccine,  they  did  mitigate  the  course  of  the  diseases.  The  more 
sensitive  complement  fixation  test,  moreover,  shared  one  major  weak- 
ness with  the  Weil-Felix  test:  both  were  diagnostic  only  when  antibody 
levels  rose  during  the  course  of  the  illness.  Neither  was  of  value  at  the 
time  a  patient  first  became  ill.  For  more  than  three  decades  after  Cox's 
discovery,  however,  his  method  remained  the  standard  procedure  for 
producing  spotted  fever  vaccine,  and  the  complement  fixation  test 
stood  as  the  diagnostic  tool  of  choice  for  rickettsial  diseases.  With  the 
versatile  egg.  Cox  accompHshed  his  goal,  freeing  vaccine  production 
from  the  danger  and  expense  entailed  in  the  tick  tissue  method  and 
opening  wide  new  horizons  for  research  on  rickettsiae  when  World 
War  II  ended. 


Chapter  Ten 


Spotted  Fever  Therapy, 
from  Sage  Tea  to 
Tetracycline 

Many  methods  of  treatment  have  been  advised  and  employed  in  the 
attempt  to  cure  this  disease.  They  run  the  gamut  of  the  Pharmacopoeia 
from  sage  tea  to  quinine  and  they  have  returned  to  that  tacit  admission  of 
ignorance,  "good  nursing  and  symptomatic  medication." 

William  Colby  Rucker,  19 12 


"The  desire  to  take  medicine,"  wrote  William  Osier  of  the  Johns 
Hopkins  University  School  of  Medicine,  "is  perhaps  the  greatest  feature 
which  distinguishes  man  from  animals."^  Whether  folk  remedies,  pat- 
ent medicines,  or  compounds  from  orthodox  pharmacopeias,  all  sorts 
of  pills,  powders,  Hquids,  and  potions  have  been  ingested  by  victims 
of  disease  in  their  quest  to  cure  their  sufferings.  They  have  also  sub- 
mitted to  being  bled,  purged,  vomited,  and  sweated.  They  have  extolled 
water,  hot  or  cold,  placed  their  trust  in  injections  or  faith  healers,  and 
succumbed  to  the  promises  of  quacks.  Those  people  unlucky  enough 
to  contract  Rocky  Mountain  spotted  fever  were  no  different.  Because 
this  disease  was  not  identified  until  after  the  bacteriological  revolution, 
however,  the  search  for  an  effective  therapy  against  it  was  infused  with 
the  positivism  that  has  characterized  twentieth-century  medical  science. 
Early  spotted  fever  investigators  were  inspired  by  the  dramatic  cures 
discovered  for  diphtheria  and  tetanus  and  hoped  for  a  similar  break- 
through. None  expressed  hopelessness  even  as  therapy  after  therapy 
failed  to  elicit  a  response. 

Unhke  many  diseases  known  for  centuries,  spotted  fever  was  never 
generally  viewed  as  a  manifestation  of  God's  wrath  against  sinners.^ 
Even  before  the  tick-borne  nature  of  spotted  fever  had  been  established, 
the  disease  was  not  considered  contagious,  and  its  victims  were  thus 
spared  long  quarantines  like  those  that  confined  diphtheria  and  small- 


197 


198 


Rocky  Mountain  Spotted  Fever 


pox  patients.  The  history  of  spotted  fever  is  different  in  this  sense  from 
air-  or  water-borne  diseases,  which  often  inspired  widespread  fear  of 
frequenting  pubHc  places  and  generated  antagonism  against  groups 
rumored  to  be  the  source  of  the  disease.  FaUing  property  values  in 
infected  areas  and  agitation  against  the  establishment  of  a  laboratory 
in  the  noninfected  district  did  indeed  cause  unrest  in  the  Bitterroot 
Valley.  Spotted  fever's  geographical  limitation  to  specific  areas  and  its 
certain  Hnk  to  ticks,  however,  precluded  a  sense  of  national  peril  against 
an  unknown  terror.  Unhke  the  disease  itself,  the  optimism  of  scientific 
medicine  was  contagious— from  the  beginning  of  scientific  inves- 
tigations in  1902,  people  at  risk  in  the  Bitterroot  Valley  were  con- 
vinced that  research  would  eventually  produce  a  therapy  for  their  dread 
disease.^ 

Like  the  researchers  who  had  preceded  him,  Thomas  B.  McClintic, 
the  U.S.  Public  Health  Service  investigator  who  lost  his  hfe  to  spotted 
fever  in  August  19 12,  examined  potential  cures  for  the  disease.  During 
the  fall  and  winter  of  1911-1912,  while  he  worked  in  Washington  at 
the  Hygienic  Laboratory,  McClintic  decided  to  investigate  the  thera- 
peutic potential  of  arsenical  compounds.  Treatment  with  these  sub- 
stances had  received  a  boost  in  19 10,  when  Paul  EhrHch  introduced 
the  arsenical  he  called  Salvarsan  as  the  first  effective  specific  against 
the  trypanosome  of  syphiHs.  Not  surprisingly,  arsenic  compounds  soon 
were  widely  employed  by  physicians  hoping  that  they  might  also  be 
a  "magic  bullet"  against  other  diseases.  McCHntic,  moreover,  had 
recently  learned  from  a  Stevensville,  Montana,  physician  that  two 
spotted  fever  victims  recovered  after  receiving  sodium  cacodylate,  an 
antimalarial  arsenical.  His  research  with  arsenicals,  he  noted,  was 
theoretically  based  on  "some  indications  pointing  to  the  infection  of 
spotted  fever  being  protozoal  in  character."  He  thus  chose  to  treat 
guinea  pigs  and  rhesus  monkeys  with  those  arsenicals  known  to  have 
a  toxic  effect  on  protozoan  organisms."^ 

In  addition  to  sodium  cacodylate,  he  tried  Salvarsan  itself  and  hex- 
amethylenamine,  a  urinary  tract  bactericide  known  by  its  trade  name, 
Urotropin.  In  order  to  test  both  the  therapeutic  and  prophylactic  pow- 
ers of  the  drugs,  he  administered  doses  to  some  of  his  experimental 
animals  at  the  time  they  were  inoculated  with  spotted  fever.  Usually, 
however,  treatment  began  when  the  temperature  of  the  animal  began 
to  rise.  His  results  were  "by  no  means"  encouraging.  "In  fact,"  he 
wrote,  "the  administration  of  the  drugs  seems,  on  the  whole  ...  to 
have  hastened  the  death  of  most  of  the  animals  that  were  treated."^ 

McClintic's  successors  experienced  similar  frustrations.  In  191 8, 
S.  Burt  Wolbach  reported  to  the  chairmen  of  the  Montana  State  Boards 


spotted  Fever  Therapy 


199 


of  Health  and  Entomology  that  he  had  conducted  experiments  on  the 
therapeutic  value  of  an  antimony  compound  with  negative  results. 
Like  McClintic,  he  observed  that  the  hoped-for  therapy  actually  had 
"a  deleterious  influence"  and  accented  the  vascular  lesions  in  exper- 
imental animals.  During  the  1920s,  Roscoe  R.  Spencer  worked  with 
salts  of  bismuth.  In  his  1923  annual  report,  he  Hkewise  concluded  that 
these  "chemotherapy  experiments  . . .  have  yielded  no  striking  results."^ 

If  these  researchers  sought  a  magic  bullet  that  would  selectively  kill 
spotted  fever  organisms,  others  adopted  what  might  be  described  as 
the  shotgun  approach  of  internal  antiseptics.  In  1924,  H.  P.  Greeley, 
a  physician  from  Madison,  Wisconsin,  speculated  that  "tick  fever" 
might  be  more  responsive  to  intravenous  medications  "because  of  its 
pathology."  Greeley's  logic,  based  on  his  knowledge  that  spotted  fever 
attacked  the  capillaries,  led  him  to  treat  a  twenty-eight-year-old  woman 
by  injecting  20  cc  of  a  i  percent  solution  of  Mercurochrome-220 
soluble  intravenously.  "Within  an  hour,"  he  noted,  "there  was  a  severe 
chill,  and  following  it  the  temperature  rose  to  104.8°  F.  Within  six 
hours,  the  muscular  pains  and  soreness  began  to  leave."  Although  he 
admitted  that  one  case  did  not  prove  his  argument,  he  called  for  further 
trials  of  the  chemical.^ 

Greeley's  logic  was  characteristic  of  the  type  that  underlay  many 
spotted  fever  drug  tests.  If  a  drug  was  known  to  be  efficacious  for  a 
disease  having  some  symptoms  in  common  with  spotted  fever,  it  seemed 
reasonable  to  test  it.  Such  was  the  case  in  1926,  when  a  Dr.  Henline 
suggested  that  Ralph  R.  Parker  try  Caprokol,  the  trade  name  for 
hexylresorcinol,  another  urinary  tract  antiseptic  also  used  against 
hookworms  and  roundworms.  Since  kidney  failure  sometimes  accom- 
panied spotted  fever,  Parker  observed  that  it  might  "be  worth  while 
to  try  this  out."  Similarly,  L.  C.  Fisher  of  the  Department  of  Medicine 
of  the  University  of  Minnesota  reasoned  that  the  nature  of  the  vascular 
lesions  and  the  localization  of  the  virus  in  the  endothelium  suggested 
that  spotted  fever  might  respond  to  intravenous  chemotherapy.  Im- 
pressed by  British  reports  that  "various  colloidal  substances"  effec- 
tively modified  the  course  of  experimental  typhus  if  given  early.  Fisher 
tested  new  drugs  of  this  type:  "Germanin  (Bayer  205),  metaphen, 
triphal  (organic  gold  compound),  and  tryparsamide."  None  proved 
any  better  than  earlier  drugs  in  protecting  guinea  pigs  against  spotted 
fever.  ^ 

Whenever  scientific  progress  seems  thwarted  at  every  turn  by  the 
mysteries  of  disease,  folk  and  quack  remedies  enjoy  a  surge  of  pop- 
ularity.^ The  failure  of  medical  science  to  uncover  an  effective  cure  for 
Rocky  Mountain  spotted  fever  encouraged  many  people  to  take  ther- 


200 


Rocky  Mountain  Spotted  Fever 


apy  into  their  own  hands.  Unorthodox  and  quack  treatments,  based 
primarily  on  the  post  hoc,  ergo  propter  hoc  fallacy,  abetted  by  the 
fear  of  an  uncontrollable  danger,  and  nearly  always  promoted  with 
bold  promises  backed  up  with  the  mere  pretense  of  evidence,  took 
many  forms.  In  191 6,  for  instance,  a  Dr.  Fox  of  Arco,  Idaho,  claimed 
to  have  discovered  a  "mixture  of  medicines  which  thru  actual  tests 
already  made  shows  that  it  will  abrupt  a  case  of  Rocky  Mountain  tick 
fever  in  five  days."  Dr.  Fox  based  his  claim  to  efficacy  on  the  fact  that 
five  spotted  fever  victims  recovered  after  taking  his  unnamed  mixture. 
Patient  number  six  may  not  have  been  so  lucky,  for  nothing  further 
was  heard  of  Dr.  Fox  and  his  remedy. 

Advocates  of  other  proposed  therapies  clothed  their  claims  in  the 
findings  of  bacteriology,  promoting  their  products  as  "germ  killers." 
In  1 94 1,  one  such  product,  manufactured  by  a  family  in  Forest  Grove, 
Montana,  and  known  only  as  "the  remedy,"  was  sent  to  the  Rocky 
Mountain  Laboratory  for  testing.  "The  remedy  is  a  Hquid,"  wrote 
Martin  J.  Elam  in  his  accompanying  letter.  Because  it  contained  "sev- 
eral ingredients,  one  being  a  poison,"  he  instructed,  it  was  "to  be 
applied  externally."  Claiming  that  his  nostrum  was  "an  efficient  germ 
killer,"  Elam  asserted  that  it  had  cured  his  friends  and  neighbors  of 
"blood  poisoning,  pink  eye,  insect  stings  and  bites,  infected  tick  bites," 
while  having  "no  harsh  effect  on  sores  or  the  mucus  membrane."^ ^ 

An  even  longer  list  of  diseases  was  purportedly  cured  by  a  patent 
medicine  similarly  marketed  as  an  external  germ  killer.  Sold  by  the 
Triangle  Drug  Company  in  Edgerton,  Wyoming,  the  C.Y.T.  Tick  Bite 
and  Blood  Poison  Remedy  was  certified  as  effective  for  blood  poison, 
snake  bite,  tick  bite,  toothache,  gout,  eczema,  bunions,  frostbite  and 
chilblains,  barbers'  itch,  ringworms,  carbuncles,  boils  and  warts,  in- 
growing toenails,  rusty  nail  punctures,  and  bee  and  insect  bites.  Such 
a  wonder  drug  deserved  exceptional  advertising,  and  its  handbill  un- 
abashedly proclaimed  C.Y.T.  to  be  "The  Greatest  Discovery  of  the 
Twentieth  Century  for  Men,  Women,  and  Children."  A  separate  page 
was  required  for  the  large  number  of  testimonials  from  happy  cus- 
tomers. Adopting  the  cautionary  style  of  orthodox  medicine,  C.Y.T.'s 
handbill  writers  featured  the  word  poison  in  large  letters,  gave  direc- 
tions for  the  user  "to  rub  in  some  vaseline  or  some  good  grade  cold 
cream"  after  applying,  and  included  this  admonition  in  boldface  type: 
"Do  not  apply  after  the  inflammation  and  pain  has  been  stopped." 
John  A.  Anderson,  president  of  Triangle  Drug  Company,  sent  a  bottle 
of  the  remedy  to  the  RML  for  testing.  Anderson  believed  that  labo- 
ratory tests  would  show  that  C.Y.T.  would  "kill  the  virus  of  Rocky 
Mountain  Spotted  Fever,  if  used  in  time.  We  advise  applying  the  med- 


spotted  Fever  Therapy 


20 1 


icine  as  soon  as  the  patient  has  been  bit  by  a  tick,  not  waiting  to  see 
if  he  has  been  bit  by  an  infected  or  a  non-poisonous  tick  and  in  such 
cases  results  have  been  excellent." 

Older  beliefs  in  the  commonality  of  all  diseases  also  contributed  to 
therapies  proposed  for  spotted  fever.  Humoral  theory,  for  example, 
held  that  an  imbalance  in  body  humors  caused  disease.  Blood  was  one 
essential  body  humor.  Since  spotted  fever  rickettsiae  had  been  dem- 
onstrated in  blood,  and  since  syphilis  was  widely  known  as  "bad 
blood,"  it  is  not  surprising  that  the  two  might  be  linked.  In  1938  an 
Idaho  man  who  styled  himself  a  "Dr  of  Naturapthie"  and  a  twelve- 
year  veteran  cowboy  in  Wyoming,  Colorado,  and  Idaho,  claimed  that 
"Spoted  [sic]  Fever  is  the  (3rd)  stage  of  Syples  [sic]  No  Person  who  is 
free  from  Syphlectic  Blood  will  Take  Spoted  Fever."^^ 

A  Wyoming  woman,  who  claimed  she  had  "the  right  to  M.D."  but 
did  not  practice,  combined  humoral  theory  and  folk  wisdom  with 
some  simple  chemistry.  Arguing  that  the  tick  "is  not  more  poisonous 
than  others  of  its  nature,  except  when  it  has  been  feeding  on  the  carrion 
of  sheep  or  other  decayed  flesh,"  she  advocated  treatment  for  a  tick 
bite  more  commonly  recommended  for  snake  bites:  "By  saturating  the 
saliva  with  tobacco,  any  friend  may  with  impunity  make  suction  over 
the  wound  by  the  mouth."  She  also  recommended  that  the  victim 
follow  this  treatment  by  using  ammonia  both  externally  and  internally, 
since  "we  find  the  bite  acts  as  an  acid  in  the  blood."  Her  main  concern 
was  the  education  of  mountaineers  and  sheepherders,  for  whom  spot- 
ted fever  was  an  occupational  hazard.  Opining  that  sheepherders  es- 
pecially needed  her  advice  because  of  their  "slothful  nature,"  she  stated: 
"In  isolated  places  I  have  proposed  the  appHcation  of  freshly  prepared 
mud,  frequently  changed,  and  much  bathing  if  near  streams.  Also  a 
free  cathartic,  with  alkaline  potions.  Much  fruit  of  a  very  acid  nature 
and  light  diet  with  plenty  of  rest.  The  nightly  removal  of  all  clothing 
and  the  running  of  the  hand  over  the  body  would  warn  us  of  the  tick's 
presence  in  ample  time  for  quick  treatment  and  save  many  lives. "^"^ 

Occasionally,  unorthodox  remedies  were  bizarre.  One  married  cou- 
ple who  contracted  the  disease  in  Idaho  attributed  their  recoveries  to 
the  ministrations  of  a  Chinese  doctor.  The  doctor,  wrote  the  wife, 
"didn't  come  near  the  bed"  but  prescribed  that  they  steep  the  teeth 
and  toenails  of  a  Chinaman  in  water  to  produce  a  curative  brew.  "I 
was  to  take  V2  cup  at  10  o'clock  each  day  for  3  days,"  she  stated, 
"and  after  10  days  or  more  I  got  up,  but  was  never  so  weak  in  my 
life."^^ 

The  exaltation  of  the  common  man  with  common  sense  contributed 
to  another  line  of  therapy  in  spotted  fever.  Representing  one  basic 


202 


Rocky  Mountain  Spotted  Fever 


commonsense  approach  was  Knute  F.  Turnquist,  who  suffered  from 
the  disease  in  Lo  Lo,  Montana,  in  1906.  Turnquist's  self-designed 
treatment  was  direct  and  simple:  he  stayed  drunk  for  two  days.  More 
often  the  commonsense  approach  was  reflected  in  hope  that  an  effective 
cure  might  lie  in  some  familiar  substance  simply  overlooked  by  the 
scientific  community.  And  indeed,  for  a  brief  time  in  Montana,  bicar- 
bonate of  soda  — ordinary  baking  soda— was  thought  to  be  the  simple, 
surprise  cure  for  spotted  fever  that  no  one  had  thought  to  investigate, 
because  a  number  of  patients  recovered  after  being  treated  with  it. 
During  the  devastating  19  21  tick  season,  however,  when  all  eleven 
victims  of  spotted  fever  died,  earlier  hopes  were  dashed.  A  dejected 
Robert  A.  Cooley  wrote  in  response  to  an  inquiry  about  the  treatment 
from  a  University  of  Nevada  professor  who  had  earlier  visited  Mon- 
tana: "At  the  time  you  were  here  the  matter  of  bicarbonate  of  soda 
as  a  treatment  for  spotted  fever  was  very  much  in  our  minds  because 
of  some  recent  experiences.  It  so  happened  that  we  had  an  unusual 
number  of  cases  this  year  and  this  treatment  was  tried  in  a  number 
of  instances.  The  further  experience  we  had  was  quite  discouraging. 
The  best  we  can  say  now  is  that  there  is  a  possibility  that  it  may  be 
of  some  value. "^^ 

Many  people  relied  on  folk  remedies  when  they  or  their  relatives 
fell  ill  with  spotted  fever.  Far  and  away  the  most  widely  recommended 
was  tea  made  from  sagebrush.  The  use  of  sage  tea,  a  woman  from 
Washington  State  wrote  to  the  RML,  "is  so  simple  you  perhaps  will 
think  it  a  joke  but  I'm  very  sure  it  will  work."^^  As  proof  of  efficacy 
she  cited  the  successful  recovery  of  her  sister  and  husband  at  different 
times.  From  Nebraska  came  a  similar  letter  hailing  the  medicinal  qual- 
ities of  sage  tea:  "Have  you  found  a  cure  for  the  Rocky  Mountain 
spotted  fever?  If  not  will  you  try  this  tea:  take  the  bark  from  the  Idaho 
sage  brush  and  make  a  medium  strong  tea.  .  .  .  The  tea  cured  an  uncle 
of  mine  in  Idaho. "^^  So  many  letters  suggesting  the  use  of  sage  tea 
arrived  at  the  laboratory,  in  fact,  that  Ralph  R.  Parker,  whose  duties 
included  answering  each  letter,  commented  to  a  friend:  "Of  course,  it 
has  been  laughed  at,  but  actually  I  know  of  no  attempt  to  determine 
if  it  does  have  value.  Personally,  I  doubt  it  but  my  doubt  is  not  backed 
by  any  evidence.  I  may  get  reckless  some  time  and  try  it  on  a  few 
guinea  pigs.  If  spotted  fever  shouldn't  kill  them,  perhaps  the  tea  will."^^ 

Most  advocates  of  sage  tea  pressed  their  cases  on  humanitarian 
grounds.  "I  just  won't  feel  right  keeping  it  to  myself  in  case  it  would 
help  some  one,"  stated  one  correspondent.^^  Many  other  people,  how- 
ever, sought  compensation  from  the  federal  government  for  their  as- 
sistance. Especially  during  the  Great  Depression,  people  seemed  to  feel 


spotted  Fever  Therapy 


203 


justified  in  asking  for  a  portion  of  New  Deal  largess.  In  1936,  Thomas 
C.  Cooper  of  Helena,  Montana,  offered  to  tell  the  laboratory  a  secret 
about  the  origins  of  wood  ticks.  "I  just  happen  to  stumble  upon  the 
original  insect  that  turns  into  a  wood  tick  last  fall  and  this  spring,  I 
have  positive  proof  that  I  am  correct."^^  Having  answered  Cooper's 
letter  in  appropriately  noncommittal  but  respectful  language,  Parker 
received  a  second  missive  requesting  money. 

If  I  was  financially  situated  so  that  it  was  possible,  I  would  only  be  too  glad 
to  divulge  this  secret  just  for  humaritarian  [sic]  sake,  however,  inasmuch  as 
the  government  is  spending  money  with  its  boondoggling  ideas  for  much  less 
important  things  than  this,  and  also  inasmuch  as  I  am  in  my  declining  years 
now  I  see  no  reason  why  the  government  should  not  pay  me  for  something 
that  will  benefit  its  citizens  in  health  the  most  important  of  all  things.  .  .  . 
Awaiting  further  word  from  you.^^ 

Although  Parker  always  explained  that  the  government  would  not 
pay  for  information  or  treatments,  he  often  offered  to  subject  proposed 
therapies  to  analysis  and  testing  at  the  RML.  Many  such  offers  were 
refused,  but  a  number  of  preparations  were  indeed  tested.  In  1941, 
James  Sproat,  a  physician  in  Portland,  Oregon,  sent  one  hundred 
ampules  of  a  solution  he  claimed  would  cure  spotted  fever  and  a  variety 
of  other  maladies.  "Should  the  solution  turn  amber  in  color,"  stated 
his  accompanying  letter,  "there  is  no  cause  for  alarm  as  its  efficacy  is 
not  effected  [sic]  in  the  least."  Sproat  commented  that  "the  normal 
adult  dose  is  30  c.c.  daily,"  injected  intravenously,  but  he  observed 
that  a  physician  should  exercise  his  own  judgment  about  the  efficacious 
dosage.  "In  treating  chronic  conditions,  i.e.,  osteomyelitis  and  some 
forms  of  arthritis,  over  a  long  period  of  time,  I  have  found  the  best 
dosage  to  be  30  c.c.  every  twenty-four  hours.  But  in  acute  infections, 
i.e.,  carbuncles,  infected  wounds,  erysipilis  [sic]  and  similar  acute  in- 
fections, ...  I  have  given  ...  as  high  as  4  or  5  doses  of  30  c.c.  each 
in  twenty-four  hours. "^^  Presumably  the  liquid  failed  to  stand  up  under 
the  laboratory's  controlled  tests,  for  nothing  further  was  heard  of  it. 

Parker  gathered  two  large  files  of  folk,  quack,  freak,  and  mercenary 
letters  relating  to  spotted  fever  therapy.  It  is  significant,  however,  that 
the  disease  generated  no  major  therapeutic  scandal.  Spotted  fever's 
geographical  isolation  and  relatively  low  incidence  militated  against 
widespread  exploitation  of  victims.  Furthermore,  unlike  chronic  dis- 
eases in  which  the  placebo  effect  often  fooled  patients  into  believing 
that  quack  therapies  were  efficacious,  spotted  fever  ran  a  severe  and 
unmitigated  course  from  onset  to  recovery  or  to  death. 

By  the  early  1930s  nearly  all  investigators  were  disheartened  about 
the  prospects  for  discovering  new  chemical  agents  against  infectious 


204 


Rocky  Mountain  Spotted  Fever 


diseases.  Not  since  the  introduction  of  Paul  Erhlich's  Salvarsan  had  a 
chemical  magic  bullet  been  found  that  was  effective  against  infectious 
diseases.  One  bright  ray  of  hope  broke  into  the  dismal  therapeutic 
situation  during  the  late  1930s:  the  discovery  of  the  powerful  sulfon- 
amide drugs. In  1935,  Gerhardt  Domagk,  director  of  research  in 
experimental  pathology  and  bacteriology  at  the  research  laboratories 
of  the  I.  G.  Farben  Industrie  in  Elberfeld,  Germany,  announced  that 
a  red  dye  called  Prontosil  would  cure  mice  of  a  lethal  infection  with 
hemolytic  streptococci.  The  following  year  a  British  team  got  dramatic 
results  with  the  drug  in  the  treatment  of  streptococcal  childbed  fever. 
The  active  agent  of  the  trademarked  drug  was  soon  found  to  be  sul- 
fanilamide, and  shortly  afterward  other  sulfa  derivatives  were  man- 
ufactured. The  new  sulfa  drugs  were  hailed  widely  as  wonder  drugs, 
and  even  the  editors  of  the  generally  restrained  Science  magazine 
echoed  public  optimism  when  they  headlined  a  story  on  sulfas  "Hope 
of  Curing  Tuberculosis,  Influenza,  and  Leprosy."^^ 

At  the  National  Institute  of  Health  in  Bethesda,  Maryland,  Norman 
H.  Topping  set  about  testing  the  effectiveness  of  Prontosil  and  sulfa- 
pyridine  against  spotted  fever  and  endemic  typhus.  "Since  chemo- 
therapy is  being  used  so  extensively  in  the  treatment  of  a  wide  variety 
of  infectious  diseases,  it  was  believed  advisable  to  test  in  the  laboratory 
the  action  of  two  of  the  most  popular  chemotherapeutic  agents,"  he 
observed.  His  hopes,  as  well  as  those  of  people  living  in  areas  where 
spotted  fever  was  prevalent,  were  dashed  by  the  results  of  the  exper- 
iments. Not  only  did  the  drugs  have  no  positive  effect  on  the  course 
of  either  disease,  but  experimental  animals  treated  with  the  sulfa  drugs 
died  sooner  than  control  animals.  "These  experiments  indicate,"  Top- 
ping wrote  after  his  research,  "that  these  two  drugs  should  not  be  used 
in  the  treatment  of  typhus  and  Rocky  Mountain  spotted  fever."  As 
new  varieties  of  the  sulfa  drugs  were  synthesized  in  the  early  1940s, 
Ralph  R.  Parker  and  his  colleagues  at  the  RML  tested  them  all— 
sulfathiazole,  sodium  sulfathiazole,  sulfaguanidine,  and  sulfadiazine— 
with  equally  disappointing  results.  During  this  same  period,  Parker 
also  tested  two  other  drugs  developed  for  wartime  uses.  Unfortunately, 
neither  the  antimalarial  agent  atabrine  nor  a  promising  antibiotic  sub- 
stance tyrothricin  protected  guinea  pigs  from  spotted  fever. 

The  results  of  such  experiments,  however,  did  not  always  affect  the 
way  practicing  physicians  treated  their  patients.  Responding  to  the 
public's  fascination  with  and  insistence  on  taking  medicine,  some  phy- 
sicians continued  to  administer  sulfa  drugs  and  other  medications  that 
had  been  demonstrated  to  be  worthless  in  treating  spotted  fever.  Top- 
ping himself  noted  this  fact  a  few  years  later  when  he  cooperated  with 


spotted  Fever  Therapy 


205 


practicing  physicians  in  conducting  a  clinical  trial  of  an  improved 
antiserum.  "Several  of  the  cases,"  he  noted,  had  "received  one  of  the 
sulfonamides;  one  case  received  intravenous  metaphen;  at  least  one 
case  received  large  doses  of  quinine;  several  had  intravenous  fluids; 
several  had  blood  transfusions;  and  one  had  intravenous  immune  hu- 
man serum. "^^ 

Because  of  the  failure  of  know^n  drugs  to  alter  the  course  of  Rocky 
Mountain  spotted  fever,  the  Spencer-Parker  vaccine,  introduced  in  the 
mid  1920s,  provided  the  only  efficacious  medical  strategy  against  the 
disease  for  more  than  tw^o  decades.  As  dependence  on  the  vaccine 
increased  in  infected  areas,  it  became  almost  mythologically  venerated. 
In  1937,  Hollywood  film  makers  seized  upon  this  American  success 
story  and  catapulted  the  tale  of  vaccine  development  into  celluloid 
immortality.  One  of  the  genre  of  1930s  and  1940s  medical  triumph 
films,  The  Green  Light  W2is  produced  by  Warner  Brothers  Studios  and 
based  loosely  on  a  Lloyd  C.  Douglas  novel  in  which  scientists  sought 
permission— a  "green  light"— to  proceed  with  vaccine  development. 
Starring  Errol  Flynn  and  Anita  Louise,  the  film  was  spiced  with  a  love 
triangle  and  a  dramatic  denouement  when  Flynn  became  a  "human 
guinea  pig"  for  the  sake  of  science.  Although  the  film  apparently  did 
well  at  the  box  office,  reviews  were  mixed.  One  critic  judged  it  a 
"pretty  good  picture,"  but  another  wished  that  it  had  been  given  a 
red  light  before  production. 

In  the  Bitterroot  Valley,  where  spotted  fever  was  especially  virulent, 
residents  took  extraordinary  precautions  in  addition  to  their  annual 
vaccinations  with  the  Spencer-Parker  vaccine.  "Every  spring  the  folks 
would  shave  the  boys'  hair  so  they  could  be  sure  no  ticks  were  attached 
to  us,"  recalled  a  native  Bitterroot  Valley  resident,  Nick  Kramis,  who 
lost  an  aunt  to  spotted  fever  and  suffered  a  bout  with  it  himself  shortly 
after  he  began  working  in  the  tick-rearing  room  at  the  RML.  Parents 
also  issued  stern  warnings  to  their  children  against  straying  into  in- 
fected areas.  "We  were  strictly  enjoined  not  to  go  on  the  west  side  of 
the  Bitterroot  River,"  stated  Richard  A.  Ormsbee,  another  native  Bit- 
terrooter.  "My  father  enforced  this  with  me,  but  I  did  not  try  to  escape 
his  interdiction,  either! "^^ 

Throughout  endemic  areas  across  the  country,  spotted  fever  and  its 
prevention  became  a  regular  spring  public  education  feature  in  many 
newspapers.^^  By  1939,  moreover,  Nick  Kramis,  then  the  photographer 
at  the  RML,  had  produced  a  film  entitled  The  Life  History  of  the 
Rocky  Mountain  Wood  Tick  that  enjoyed  wide  popularity  among  civic 
clubs  and  other  groups  who  wished  to  educate  their  members  about 
how  to  avoid  the  disease.^ ^  Lending  support  to  this  campaign,  Parker 


2o6 


Rocky  Mountain  Spotted  Fever 


occasionally  published  articles  or  provided  information  to  science  wri- 
ters. In  1933  he  summarized  much  information  in  a  Special  Bulletin 
issued  by  the  Montana  State  Board  of  Health.  Infected  people,  he 
cautioned,  should  take  no  drugs  without  the  advice  of  their  physician. 
"Certain  drugs,  such  as  aspirin,  which  uninformed  persons  are  likely 
to  use,  are  deleterious  in  their  effects  and  should  be  avoided."^^  Parker 
also  noted  that  the  Spencer-Parker  vaccine  was  widely  used  as  a  treat- 
ment for  spotted  fever,  "in  spite  of  the  fact  that  it  is  not  recommended 
for  this  purpose. "^^ 

In  1944,  just  over  a  decade  later,  the  American  Medical  Association's 
popular  health  journal  Hygeia  offered  nearly  the  same  advice.  Its 
informational  spotted  fever  article  was  adorned  with  a  cartoon  of  a 
frantic  mother  calling  her  physician  for  information  after  finding  a 
tick  on  one  of  her  children.  Having  captured  the  reader's  attention, 
the  author  hsted  facts  "parents  should  know  about  ticks  and  spotted 
fever  to  protect  their  children  and  spare  themselves  anxiety."  The  article 
provided  detailed  information  about  the  epidemiology  of  spotted  fever, 
how  to  remove  and  dispose  of  ticks  properly,  and  how  residents  of  a 
"woody  section  of  a  tick-infested  area,"  could  obtain  the  vaccine.^"^ 

Reviews  of  spotted  fever  written  for  medical  audiences  in  the  late 
1930s  emphasized  that  the  recommended  treatment  was  "purely  symp- 
tomatic and  supportive."  In  such  a  paper  written  for  the  Rocky  Moun- 
tain Medical  Journal,  George  E.  Baker  admonished  physicians  against 
"an  attitude  of  helplessness  or  hopeless  inactivity."  Carefully  directed 
symptomatic  care  and  supportive  measures,  he  beHeved,  aided  patients 
in  eliminating  toxins  from  their  bodies  and  in  fighting  against  the 
invading  organism.  In  addition.  Baker  recommended  from  his  own 
experience— for  it  was  not,  he  noted,  mentioned  in  the  literature— the 
administration  of  neosalvarsan  dissolved  in  metaphen.  The  recoveries 
witnessed  using  these  drugs,  he  speculated,  might  have  been  caused 
by  "the  bactericidal  action  of  metaphen  together  with  the  spiroche- 
ticidal  action  of  neosalvarsan  upon  a  micro-organism  which  is  bac- 
terium-like in  character,  but  which  has  staining  properties  at  least 
resembling  that  of  spirochetes."^^  Plainly  the  same  logic  that  motivated 
administration  of  Mercurochrome  in  the  1920s  continued  to  inspire 
physicians  in  the  early  1940s. 

Although  chemotherapy  appeared  valueless  against  spotted  fever, 
the  development  of  Cox's  yolk  sac  method  to  cultivate  rickettsiae  in 
large  quantities  rekindled  interest  in  producing  an  antiserum  against 
the  disease.  The  medical  crisis  presented  by  World  War  II  provided 
further  impetus  for  research  on  this  long-abandoned  therapeutic  strat- 
egy. In  1940,  Norman  H.  Topping  announced  a  hyperimmune  rabbit 


spotted  Fever  Therapy 


207 


Norman  H.  Topping's  research  on  spotted  fever  at  the  NIH  was  launched 
in  1938  when  he  fell  ill  with  a  laboratory-acquired  infection.  He  recovered 
and  made  significant  contributions  to  understanding  the  disease,  including 
key  epidemiological  studies,  work  on  the  role  of  dogs  as  carriers  of  infected 
ticks,  and  development  of  an  immune  serum  that  lowered  mortality 
considerably.  (Courtesy  of  the  National  Library  of  Medicine.) 


serum  against  Rocky  Mountain  spotted  fever  that  gave  positive  results 
in  preliminary  tests  with  guinea  pigs  and  monkeys. Over  the  next 
three  years,  v^ith  the  cooperation  of  practicing  physicians,  he  tested 
the  new  therapy  on  seventy-one  unvaccinated,  naturally  infected  pa- 
tients in  both  the  eastern  and  western  United  States.  From  the  begin- 
ning, results  appeared  promising.  The  antiserum  reduced  deaths  from 
an  expected  rate  of  18.8  percent  to  3.8  percent.^^ 

In  1 94 1,  Topping's  antiserum  received  widespread  publicity  when 
it  was  used  against  the  case  of  spotted  fever  suffered  by  J.  Frederick 
Bell,  a  twenty-six-year-old  student  in  bacteriology  who  visited  the 
Rocky  Mountain  Laboratory  in  May  to  discuss  cooperative  work 
planned  for  the  coming  year.  Because  of  a  change  in  the  timing  of  his 
visit,  Bell  was  not  inoculated  before  his  arrival,  as  was  customary.  "As 
soon  as  I  thought  to  ask  him  about  spotted  fever  vaccination,"  Ralph 


208 


Rocky  Mountain  Spotted  Fever 


R.  Parker  noted,  "he  received  one  injection."^^  Although  Bell  was  not 
exposed  to  potentially  dangerous  areas  of  the  laboratory,  Parker  was 
uneasy  about  the  breach  of  routine  requiring  immunization  of  all 
visitors.  Subsequent  events  underscored  the  reason  for  Parker's  caution. 

On  1 6  May,  Bell  started  east  in  the  company  of  his  brother-in-law 
Carl  Larson,  who  later  became  director  of  the  Rocky  Mountain  Lab- 
oratory. When  they  reached  Rapid  City,  South  Dakota,  Bell  entered 
the  hospital  with  high  fever,  severe  headache,  general  aching,  and 
photophobia.^^  Since  he  had  no  rash,  Q  fever  or  typhus  was  originally 
suspected.  "One  day  a  beautiful  young  nurse  came  in  and  gave  me  a 
sponge  bath,"  Bell  recalled  in  a  later  interview.  "After  she  left  I  looked 
down  at  my  wrists  and  arms  and  there  I  could  see  the  spots."  He  rang 
the  bell  to  summon  her  back,  whereupon  he  pronounced  his  own 
diagnosis:  "I  know  what  I've  got  at  last— I've  got  Rocky  Mountain 
spotted  fever."^^  When  the  RML  was  informed  of  Bell's  condition, 
Parker  rushed  60  cc  of  Topping's  experimental  antiserum  to  the  at- 
tending physician.  Bell  responded  well,  and  newspapers  in  South  Da- 
kota, Minnesota,  and  Iowa  picked  up  the  medical  news,  hailing  the 
"New  Serum"  that  rendered  a  "speedy  cure"  of  Bell's  illness.  As  a 
result,  inquiries  poured  into  the  laboratory."^^ 

Because  epidemic  typhus  was  of  such  great  concern  in  194 1,  a  similar 
antiserum  was  soon  prepared  to  combat  it  as  well.  During  the  1943 
typhus  epidemic  in  Egypt,  described  as  one  of  the  most  severe  that  the 
country  had  experienced,  this  typhus  antiserum  was  among  the  ther- 
apies studied  by  members  of  the  U.S.A.  Typhus  Commission.  Results 
of  this  test  were  similar  to  those  in  the  spotted  fever  trials. Both 
spotted  fever  and  typhus  antisera  were  limited  by  the  requirement  that 
they  be  administered  early  in  the  course  of  a  disease,  preferably  before 
the  third  day.  Even  so,  they  were  the  first  therapeutic  agents  to  make 
a  clear  difference  in  the  prognosis  of  patients. 

While  these  studies  were  taking  place,  a  new  rickettsial  menace,  long 
known  to  the  Japanese  as  tsutsugamushi  but  called  scrub  typhus  by 
U.S.  troops,  threatened  the  Allied  countermove  to  stem  the  Japanese 
advance  in  the  Pacific.  James  J.  Sapero  and  Fred  A.  Butler  of  the  U.S. 
Navy  described  the  situation  early  in  1942,  when  U.S.  forces  began 
to  occupy  "numerous  widely  separated  tropical  islands  throughout  a 
vast  subequatorial  region."  Although  the  area  was  known  to  be  a 
hyperendemic  focus  of  disease,  most  medical  officers  were  unfamiHar 
with  scrub  typhus  and  other  exotic  tropical  maladies  such  as  malaria, 
dengue,  dysentery,  yaws,  filariasis,  and  leprosy.  "There  followed,  as  a 
consequence,"  observed  Sapero  and  Butler,  "a  series  of  outbreaks  of 
tropical  diseases  in  epidemic  proportions  of  a  magnitude  and  potential 


spotted  Fever  Therapy 


209 


threat  seldom  if  ever  exceeded  in  American  military  history.'"^^ 

Scrub  typhus,  one  of  the  most  serious  of  these  diseases,  disabled 
some  18,000  Allied  troops,  including  6,685  U.S.  servicemen  between 
January  1943  and  August  1945.  Fatality  rates  varied  from  a  lov^  of 
0.6  percent  in  some  regions  to  as  high  as  35  percent  in  others;  there 
were  234  deaths  among  U.S.  troops. "^"^  Japanese  miHtary  forces  suffered 
less  from  tsutsugamushi,  doubtless  because  the  endemic  disease  v^as 
familiar  to  Japanese  physicians  and  pubUc  health  workers.  Except  for 
the  1908  comparative  study  between  Rocky  Mountain  spotted  fever 
and  tsutsugamushi  made  by  U.S.  Army  physicians  Percy  M.  Ashburn 
and  Charles  F.  Craig,  few  western  studies  on  the  disease  had  been 
pursued.  In  contrast,  Japanese  investigators  had  continued  to  study 
the  two  diseases  into  the  1930s,  even  though  two  of  them  died  from 
laboratory-acquired  spotted  fever  infections  during  their  research.  The 
two  Japanese  who  succumbed  were  Kokyo  Sugata,  an  assistant  of 
Norio  Ogata  of  the  Chiba  Medical  College,  who  died  on  4  July  193 1; 
and  Masajiro  Nishibe,  a  professor  at  the  Niigata  Medical  College, 
who  died  on  13  August  1932."^^ 

Usually  scrub  typhus  was  diagnosed  by  clinical  observation  of  typical 
typhus-like  symptoms:  high  fever,  headache,  muscle  and  joint  pain, 
and  a  rash.  For  laboratory  confirmation,  a  Weil-Felix  test  had  been 
developed  during  the  1920s  and  1930s  by  British  researchers  and  their 
colleagues  at  the  Institute  of  Medical  Research  in  Kuala  Lumpur, 
Federated  Malay  States.  They  had  observed  that  the  sera  of  tsutsu- 
gamushi patients  reacted  positively  to  the  OX-K  strain  of  B.  proteus 
and  negatively  to  the  OX- 19  strain."^^ 

The  U.S.A.  Typhus  Commission  began  to  study  scrub  typhus,  noted 
its  director,  Stanhope  Bayne-Jones,  "because  of  its  last  name. . . .  When 
we  took  in  scrub  typhus,  no  one  stopped  to  ask  whether  the  Executive 
Order  apphed  or  not."  Because  it  caused  so  many  disabihties  and 
deaths  among  Allied  troops,  the  Typhus  Commission  brought  in  a 
variety  of  experts  to  attack  this  capricious  malady,  which  often  struck 
one  group  of  soldiers  while  leaving  others  nearby  untouched.  Cornelius 
B.  Philip  and  Glen  Kohls,  entomologists  who  had  left  the  RML  to  join 
the  military  after  war  broke  out,  sought  to  identify  arthropod  vectors 
of  the  disease,  which  had  been  suspected  because  victims  exhibited  an 
eschar,  or  initial  lesion,  a  characteristic  of  the  more  famiHar  European 
tick-borne  disease,  boutonneuse  fever.  Francis  G.  Blake,  dean  of  the 
Yale  University  School  of  Medicine,  and  Kenneth  F.  Maxcy,  professor 
of  epidemiology  at  Johns  Hopkins  School  of  Hygiene  and  Public 
Health,  investigated  the  epidemiology  and  medical  treatment  of  the 
disease."^^ 


2IO 


Rocky  Mountain  Spotted  Fever 


By  the  end  of  the  war,  two  major  Hnes  of  defense  against  scrub 
typhus  had  been  developed.  First,  the  U.S.  Army  launched  preventive 
education  efforts,  including  posters  describing  the  mite,  where  it  was 
likely  to  be  found,  and  how  soldiers  should  prepare  their  campsites 
to  avoid  it.  Second,  investigators  funded  by  the  Medical  Research 
Committee  of  the  Office  of  Scientific  Research  and  Development  de- 
veloped chemicals  to  impregnate  clothing  that  would  repel  the  tsut- 
sugamushi  mite.  Dimethyl  phthalate  was  initially  chosen,  but  in  1945 
the  War  Department  replaced  it  with  benzyl  benzoate,  because  it  would 
withstand  more  launderings  before  having  to  be  reapplied.  Even  so, 
soldiers'  clothing  had  to  be  retreated  every  two  weeks. 

Military  physicians  who  cared  for  scrub  typhus  victims  adopted 
supportive  therapy  like  that  used  for  years  against  Rocky  Mountain 
spotted  fever.  Norman  H.  Topping  believed  that  an  antiserum  should 
be  effective  for  treatment  and  perhaps  even  for  prophylaxis  of  scrub 
typhus.  With  the  eschar  as  an  early  diagnostic  feature,  Topping  rea- 
soned, antiserum  could  be  given  earher  and  with  greater  benefit.  By 
1945  he  had  prepared  one  that  gave  promising  results  in  mice.  Research 
by  the  U.S.  Army,  U.S.  Navy,  and  U.S.  Public  Health  Service  also 
focused  on  the  development  of  a  vaccine  against  the  disease.  Before 
either  vaccine  or  antiserum  could  be  tested,  however,  the  war  ended."^^ 

A  similar  situation  occurred  in  the  Mediterranean  theater  with  yet 
another  rickettsial  disease.  During  the  winter  of  1944  and  spring  of 
1945,  Alhed  troops  in  this  region  fell  ill  with  a  malady  first  termed 
the  Balkan  grippe  but  soon  shown  to  be  Q  fever.  The  sudden  ap- 
pearance of  this  disease  in  the  Mediterranean  area  foreshadowed  later 
findings  that  it  was  widespread  around  the  globe,  rather  than  confined 
to  Australia  and  to  the  western  United  States,  as  had  been  believed 
when  it  was  first  discovered. 

Experience  with  all  the  rickettsial  diseases  during  World  War  II  led 
to  a  much  more  specific  understanding  of  their  pathologic  mechanisms. 
In  contrast  to  earlier  observations,  which  were  generally  limited  to 
descriptions  of  damage  to  particular  tissues,  wartime  physiological 
research  illuminated  the  dynamic  biological  mechanisms  involved.  In 
1944,  Theodore  E.  Woodward  and  Edward  F.  Bland,  members  of  the 
U.S.A.  Typhus  Commission,  reported  that  studies  of  typhus  in  French 
Morocco  had  revealed  the  "overwhelming  generalized  involvement" 
of  the  peripheral  circulatory  system.  Rickettsiae  invaded  the  entire 
circulatory  tree,  causing  swelling  of  the  endothehal  cells.  By  occluding 
blood  flow,  they  gave  rise  to  the  formation  of  clots  in  the  smaller  and 
occasionally  even  the  larger  blood  vessels.  This  damage  produced  "an 
increase  of  capillary  permeability,"  which  altered  the  electrolytic  com- 


spotted  Fever  Therapy 


211 


position  of  the  blood  and  lowered  the  osmotic  pressure  as  plasma 
proteins  escaped  into  the  tissues.  These  phenomena  further  starved  the 
capillaries  of  needed  oxygen  and  nutrients,  thus  setting  up  a  vicious 
cycle  that  culminated  in  circulatory  failure/^ 

To  combat  this  v^idespread  damage,  aggressive  supportive  therapy 
was  indicated.  The  same  year  that  Woodward  and  Bland  published 
their  prescription  for  typhus  therapy,  a  North  Carolina  physician, 
George  T.  Harrell,  and  his  colleagues  outlined  a  similar  program  for 
the  treatment  of  Rocky  Mountain  spotted  fever.  Unlike  the  undiffer- 
entiated "good  nursing"  recommendations  of  earlier  decades,  the  sup- 
portive therapies  advocated  by  both  groups  were  highly  specific:  ad- 
equate fluid  intake,  blood  plasma  transfusions  if  necessary,  ammonium 
or  sodium  salts  to  improve  hypochloremia,  a  nourishing  protein  and 
carbohydrate  diet,  and  abandonment  of  the  common  practice  of  ad- 
ministering digitalis  to  stimulate  the  heart  except  to  treat  critical  heart 
problems. 

Such  a  program  was  unfortunately  necessary  because  the  most  stun- 
ning medical  triumph  of  the  war  years — the  development  of  penicillin  — 
had  proved  valueless  against  the  rickettsial  diseases.  Discovered  in 
1928  by  Alexander  Fleming,  the  mold  Penicillium  notatum  had  been 
largely  ignored  until  an  expensive  cooperative  effort  between  phar- 
maceutical firms  and  the  U.S.  government  made  large-scale  production 
possible. By  1943  tests  in  several  civiHan  hospitals  had  demonstrated 
penicillin's  potency  against  a  host  of  infections.  Not  a  chemical  com- 
pound like  the  sulfa  drugs,  this  antibiotic  was  a  substance  produced 
by  living  organisms  that  was  antagonistic  to  the  growth  of  many 
bacteria.  Here,  at  last,  was  the  long-sought  "magic  bullet"  that  cured 
staphylococcal  infections,  pneumococcal  pneumonia,  rheumatic  fever, 
syphilis,  and  gonorrhea. 

Tests  of  the  effectiveness  of  penicillin  against  Rocky  Mountain  spot- 
ted fever  and  other  rickettsial  diseases  were  conducted  in  1945  at  the 
Rocky  Mountain  Laboratory  and  in  the  research  laboratories  of  the 
Sharp  and  Dohme  pharmaceutical  house.  At  Sharp  and  Dohme,  Flor- 
ence K.  Fitzpatrick  treated  spotted-fever-infected  guinea  pigs  within 
forty-eight  hours  after  the  onset  of  fever.  All  the  animals  died.  Blood 
plasma  levels  of  the  drug,  she  noted,  were  sufficient  to  expect  recovery 
had  penicillin  been  of  any  value. 

Even  though  penicillin  had  proved  to  be  of  no  use  against  rickettsial 
diseases,  its  example  spurred  further  research  for  a  chemical  or  anti- 
biotic agent  that  would  supplant  the  limited  value  of  antisera.  Early 
efforts  followed  a  lead  suggested  in  1937  by  Hans  Zinsser  and  E.  B. 
Schoenbach  at  Harvard  Medical  School.  They  had  demonstrated  that 


212 


Rocky  Mountain  Spotted  Fever 


the  rate  of  intracellular  multiplication  of  rickettsiae  in  tissue  cultures 
was  determined  by  the  metabolic  rate  of  the  host  cells.  Under  conditions 
of  high  metabolic  activity,  Httle  or  no  multiplication  of  the  intracellular 
parasites  took  place.  Only  under  conditions  of  reduced  metaboUc  ac- 
tivity was  active  multiplication  noted.^^  This  information  set  investi- 
gators searching  for  a  nontoxic  substance  that  would  increase  cellular 
metabohsm  and  thereby  inhibit  rickettsial  multiplication. 

In  1942  para-aminobenzoic  acid,  commonly  called  PABA  and  gen- 
erally considered  to  be  a  vitamin,  was  identified  as  a  promising  an- 
tirickettsial  agent.  In  a  classified  report  to  the  Division  of  Medical 
Sciences  of  the  National  Research  Council,  John  C.  Snyder,  John  Maier, 
and  C.  R.  Anderson  described  its  effectiveness  in  reducing  mortaHty 
from  experimental  murine  typhus  in  white  mice.^^  A  year  later,  H.  L. 
Hamilton,  Harry  Plotz,  and  Joseph  E.  Smadel  reported  to  the  director 
of  the  U.S.A.  Typhus  Commission  on  PABA's  effect  on  the  growth  of 
typhus  rickettsiae  in  the  yolk  sac  of  the  infected  chick  embryo. 

The  first  large-scale  test  of  PABA  was  conducted  in  1943,  a  part  of 
the  therapeutic  trials  made  during  the  typhus  epidemic  in  Egypt.  The 
results  indicated  that  PABA  ameliorated  the  clinical  course  of  the  dis- 
ease if  it  was  started  during  the  first  week  of  illness.  The  drug  produced 
no  unfavorable  effects  with  the  exception  of  a  tendency  to  develop  a 
low  white  blood  cell  count,  which  could  be  monitored.  When  Andrew 
Yeomans  and  his  colleagues  published  these  findings  in  the  Journal  of 
the  American  Medical  Association,  its  editors  wondered,  "What  effect 
will  para-aminobenzoic  acid  and  related  compounds  have  on  Rocky 
Mountain  spotted  fever  and  other  rickettsial  diseases?"  That  question 
was  soon  answered.  In  1945,  Ludwik  Anigstein  and  Madero  N.  Bader 
reported  that  PABA  was  indeed  efficacious  against  spotted  fever  in 
guinea  pigs.  Shortly  thereafter,  Harry  M.  Rose  and  his  colleagues  at 
Columbia  University  College  of  Physicians  and  Surgeons  reported  the 
first  clinical  results  of  a  single  human  case  of  Rocky  Mountain  spotted 
fever  treated  with  PABA.  The  patient,  a  woman,  improved  rapidly  after 
twenty-four  hours  of  therapy.^^ 

Additional  evidence  for  the  efficacy  of  PABA  therapy  was  soon 
amassed.  The  cases  of  spotted  fever  suffered  by  a  Fairfax,  Virginia, 
couple  were  cured  with  PABA  after  they  failed  to  respond  to  immune 
rabbit  serum  therapy.  A  group  of  cases  studied  by  physicians  in  Wil- 
mington, Delaware,  indicated  that  spotted  fever  responded  even  more 
sensitively  to  PABA  than  did  typhus.  They  also,  however,  noted  the 
limitations  of  the  drug  as  reflected  in  its  failure  to  cure  a  sixty-seven- 
year-old  man  with  long-standing  renal  disease  and  a  history  of  heart 
attack.  This  case,  they  stated,  "may  serve  to  illustrate  the  point  .  .  . 


spotted  Fever  Therapy 


213 


that  p-aminobenzoic  acid  retards  or  prevents  the  spread  and  prolif- 
eration of  the  rickettsias  in  the  body  but  is  not  an  antidote  for  any 
toxin  already  released  and  does  not  repair  damage  already  done."^^ 

PABA  was  rickettsiostatic,  not  rickettsiocidal— that  is,  it  inhibited 
further  growth  of  rickettsiae  but  did  not  kill  them  outright.  Because 
of  this,  it  was  essential  that  treatment  begin  as  soon  as  possible.  Once 
the  organisms  had  damaged  the  tissues  and  multiplied  to  large  numbers, 
the  drug  could  not  stop  them.  The  giant  step  in  therapy  represented 
by  PABA,  however,  inspired  greater  confidence  than  ever  before  among 
physicians.  A  review  of  spotted  fever  written  in  1947  by  Samuel  F. 
Ravenel  reflected  this  greater  sense  of  knowledge  about  and  control 
over  the  disease  gained  during  the  war  years.  "In  the  early  days,  the 
treatment  of  this  disease  was  symptomatic,  which  simply  enabled  the 
patient  to  die  or  recover  somewhat  more  comfortably."  In  contrast, 
Ravenel  was  able  to  outline  a  comprehensive  treatment  plan  that  should 
enable  any  physician  to  do  battle  with  confidence  against  Rocky  Moun- 
tain spotted  fever.  ^° 

Although  PABA  therapy  enriched  the  physician's  armamentarium  in 
the  fight  against  spotted  fever,  it  was  soon  eclipsed  by  more  powerful 
drugs.  Unlike  the  development  of  the  Spencer-Parker  or  Cox  vaccines, 
a  cure  for  spotted  fever  did  not  emerge  from  a  direct  attack  on  the 
disease  in  isolation.  Rather,  it  resulted  from  planned,  persistent,  and 
expensive  empirical  searches  for  antibiotics  undertaken  by  pharma- 
ceutical companies.  The  example  of  penicillin  research,  with  its  large 
investment  and  larger  profits,  was  the  stimulus  for  the  effort  to  find 
antibiotics  against  other  diseases.  Not  yet  knowing  the  structure,  much 
less  the  physiology,  of  rickettsiae  or  viruses,  investigators  proceeded 
without  benefit  of  detailed  knowledge  about  the  organisms  they  were 
combating. 

Even  so,  by  the  late  1940s,  Harry  F.  Dowling  noted  in  his  compre- 
hensive study  of  infectious  disease  therapy,  Fighting  Infection^  "at  least 
half  a  dozen  companies  had  teams  of  investigators  actively  looking 
for  antibiotics."^^  One  of  them,  Parke,  Davis  and  Company,  estabfished 
a  research  grant  at  Yale  University  to  enable  Paul  Burkholder,  a  bot- 
anist, to  search  soil  samples  for  microorganisms  with  antibiotic  po- 
tentialities. He  isolated  a  promising  mold  from  Venezuelan  soil,  which 
was  subsequently  named  Streptomyces  Venezuela.  Parke,  Davis  scien- 
tists extracted  a  substance  from  it  that  inhibited  the  growth  of  a  number 
of  pathogenic  bacteria.  The  new  antibiotic  was  named  chloramphenicol 
and  given  the  trade  name  Chloromycetin.^^ 

In  their  publication  announcing  the  discovery  of  the  drug,  Parke, 
Davis  scientists  noted  that  Chloromycetin  was  more  effective  than 


214 


Rocky  Mountain  Spotted  Fever 


With  the  discovery  of  broad-spectrum  antibiotics,  Rocky  Mountain  spotted 
fever  became  a  curable  disease.  Aureomycin  and  Terramycin  were  trade 
names  for  the  tetracycline  drugs.  Chloramphenicol  was  sold  under  the 
name  Chloromycetin.  Potentially  toxic  side  effects  of  the  drugs  were  not 
recognized  for  nearly  a  decade  after  they  were  introduced.  (Courtesy  of  the 
Rocky  Mountain  Laboratories,  NIAID.) 


PABA  against  Rickettsia  prowazekii,  the  organism  that  caused  epidemic 
typhus,  in  experiments  on  chicken  embryos  and  mice.^^  They  sent 
samples  of  the  promising  drug  to  Joseph  E.  Smadel,  then  scientific 
director  of  the  Walter  Reed  Army  Institute  of  Research,  who  had  a 
"working  arrangement"  with  Parke,  Davis  to  test  "any  new  anti- 
microbial drugs  which  exerted  even  the  slightest  inhibitory  effect  for 
viral  and  rickettsial  agents. "^"^  WTien  he  got  similar  results  in  his  lab- 
oratory, Smadel  enthusiastically  recommended  immediate  trials  in  hu- 
mans. 

Shortly  thereafter,  Eugene  H.  Payne  of  Parke,  Davis  took  a  team  of 
scientists  to  Bolivia,  where  an  epidemic  of  typhus  was  raging.  The 
power  of  this  new  drug  against  typhus  was  dramatically  confirmed. 
An  anecdote  recounted  by  Dowling  bears  repeating  here  as  an  illus- 


spotted  Fever  Therapy 


215 


tration:  "In  collaboration  with  local  doctors,  .  .  .  [Payne]  treated  22 
of  the  sickest  patients,  five  of  whom  had  been  listed  as  certain  to  die. 
All  recovered,  including  one  for  whom  the  death  certificate  had  already 
been  filled  out  and  signed,  awaiting  only  the  insertion  of  the  hour  of 
death."  Smadel's  tests  of  Chloromycetin  on  typhus  patients  in  Mexico 
were  equally  successful.  He  then  arranged  with  Raymond  Lewthwaite, 
director  of  the  Institute  for  Medical  Research  at  Kuala  Lumpur,  Ma- 
laya, to  conduct  field  trials  of  the  new  antibiotic  on  scrub  typhus  cases. 
All  ninety-four  patients  treated  with  it  recovered. 

On  the  basis  of  these  spectacular  results,  Maurice  C.  Pincoffs  and 
his  colleagues  of  the  University  of  Maryland  School  of  Medicine  in 
Baltimore  cooperated  with  Joseph  E.  Smadel  of  the  Army  Medical 
School  to  test  Chloromycetin  furnished  by  Parke,  Davis  against  spotted 
fever.  Patients  were  given  tablets  of  the  drug  in  dosages  based  on  body 
weight  that  had  proved  effective  against  scrub  typhus— an  initial  large 
dose  followed  by  smaller  doses  every  three  hours.  No  toxicity  was 
observed,  but  the  researchers  noted  that  the  drug  had  not  been  used 
over  a  long  period  of  time.  The  results  of  the  therapy  were  indisputably 
positive.  Irrespective  of  the  height  of  the  preceding  fever  or  the  age  of 
the  patient,  body  temperature  fell  to  normal  within  seventy-six  hours 
after  the  initial  dose.  The  average  duration  of  fever  was  a  mere  2.2 
days.  Shortly  thereafter,  other  researchers  confirmed  these  results  and 
the  popular  press  acclaimed  Chloromycetin  as  the  "greatest  drug  since 
penicillin."^^ 

Almost  simultaneously  with  the  development  of  chloramphenicol, 
researchers  at  Lederle  Laboratories  announced  the  development  of  an 
antibiotic  from  Streptomyces  aureofaciens,  which,  because  of  its  gold 
color,  was  named  Aureomycin.  In  June  1948  a  research  group  at 
Children's  Hospital  in  Washington,  D.C.,  collaborated  with  members 
of  the  Department  of  Preventive  Medicine  at  Johns  Hopkins  University 
School  of  Medicine  to  test  Aureomycin  in  thirteen  patients  suffering 
from  Rocky  Mountain  spotted  fever.  "The  response  of  these  patients 
has  been  impressive,"  the  researchers  wrote,  "and  it  is  apparent  that 
Aureomycin  is  an  effective  therapeutic  agent."^^  Shortly  thereafter, 
researchers  at  a  third  pharmaceutical  house,  Charles  Pfizer  and  Com- 
pany, produced  another  antibiotic  effective  against  rickettsial  diseases. 
Isolated  from  Streptomyces  rimosus,  this  drug  was  called  Terramycin. 
When  the  chemical  structures  of  Aureomycin  and  Terramycin  were 
elucidated,  they  were  found  to  be  nearly  identical.  Together  they  be- 
came known  as  the  tetracyclines,  and,  with  later  analogues  and  with 
chloramphenicol,  they  were  termed  broad-spectrum  antibiotics.  These 
drugs  were  effective  not  only  against  rickettsial  infections  and  those 


zi6 


Rocky  Mountain  Spotted  Fever 


diseases  that  had  yielded  already  to  peniciUin  but  also  against  diseases 
whose  stubborn  bacterial  agents  had  resisted  all  earlier  therapies,  in- 
cluding typhoid  fever,  brucellosis,  mycoplasma  pneumonias,  and  chla- 
mydial infections. 

The  advent  of  antibiotics  effective  against  rickettsial  diseases 
crow^ned  the  av^^esome  achievements  of  scientific  and  medical  research 
during  the  1940s.  Through  research  on  the  atomic  bomb,  physicists 
had  opened  a  qualitatively  new  field  that  held  great  promise  in  medicine 
and  in  world  energy  production  while  simultaneously  threatening 
worldwide  destruction.  Atomic  power  and  antibiotics  symbolized  the 
power  of  research  that  had  also  produced  a  host  of  less-publicized 
discoveries,  from  improved  blood  transfusion  techniques  to  radar. 
These  achievements  led  many  leaders  of  the  scientific  and  medical 
communities  to  argue  forcefully  for  expanded  federal  funding  of  re- 
search, especially  in  basic  studies  that  formed  a  broad  body  of  knowl- 
edge from  which  specific  applications  might  emerge. This  effort, 
according  to  Charles  V.  Kidd,  was  "the  loudest,  most  expensive,  most 
persistent,  most  calculating,  most  emotional,  most  effective  and  socially 
useful  propaganda  campaign"  ever  mounted  on  behalf  of  science. 

Of  many  proposals,  none  was  more  far-reaching  than  that  prom- 
ulgated by  the  Committee  on  Science  and  Society  of  the  American 
Association  for  the  Advancement  of  Science.  Twelve  points  for  a  na- 
tional research  policy  emerged  from  a  symposium  held  in  December 
1944.  Point  2  called  for  "extending  systematic  research  into  every  field 
or  activity  of  life,  as  a  considered  policy  of  critically  examining  what- 
ever we  beheve  and  do,  and  proceeding  to  a  revision  of  established 
assumptions  and  practices  wherever  research  reveals  they  are  required 
or  desirable."  Point  9  went  so  far  as  to  assert  that  research  should  be 
a  coordinate  function  of  the  U.  S.  government  equal  to  the  legislative, 
executive,  and  judiciary.^^  ' 

During  the  next  decade.  Congress  and  both  Democratic  and  Re- 
publican presidents  supported  the  expansion  of  federally  sponsored 
scientific  and  medical  research— even  if  they  declined  to  grant  science 
coequal  status  under  the  Constitution.  The  National  Science  Foun- 
dation was  created,  and  the  NIH  flourished  with  the  estabfishment  of 
a  program  of  grants  to  university  researchers  and  the  creation  of  several 
new  institutes. Discussions  about  basic  and  applied  research,  more- 
over, produced  a  new  agenda  for  research  at  the  NIH.  Its  traditional 
public  health  responsibihty  of  assisting  states  with  on-site  disease  prob- 
lems, such  as  the  Rocky  Mountain  spotted  fever  work  in  Montana, 
was  transferred  to  the  newly  created  Communicable  Disease  Center, 
later  called  the  Centers  for  Disease  Control,  in  Atlanta,  Georgia.  An 


spotted  Fever  Therapy 


217 


enlarged  and  reorganized  NIH  claimed  basic  studies  as  its  mission, 
utilizing  a  document  on  postwar  science  policy  widely  known  as  the 
Steelman  Report  to  articulate  the  distinctions  between  basic  and  ap- 
plied research/^  Laboratory  studies  to  uncover  new  information  were 
generally  regarded  as  basic  research.  Gathering  statistics  on  the  inci- 
dence of  disease  fairly  clearly  fell  in  the  applied  category.  These  dis- 
tinctions, of  course,  were  somewhat  subject  to  interpretation.  Much 
epidemiological  research  and  field  studies  of  vector-borne  diseases  were 
often  difficult  to  classify. 

The  NIH  director,  Rolla  E.  Dyer,  set  about  applying  the  terms  of 
the  new  mandate  to  the  programs  of  the  several  institutes  that  com- 
prised the  now  plural  National  Institutes  of  Health.  Among  these  was 
the  National  Microbiological  Institute,  comprised  of  the  agency's  his- 
toric research  programs  in  infectious  and  tropical  diseases  and  its  work 
in  biologies  standards. Although  the  Rocky  Mountain  Laboratory 
was  made  a  coequal  branch  of  the  new  institute,  the  focus  on  basic 
research  presented  a  somewhat  awkward  problem  for  RML,  which 
had  served  during  the  war  years  principally  as  a  vaccine  factory— 
clearly  an  applied  rather  than  a  basic  function.  Furthermore,  applied 
research  was  conducted  by  its  staff  of  entomologists,  who  enjoyed  a 
worldwide  reputation  as  authorities  on  tick  taxonomy,  and  by  its 
serologists,  who  performed  laboratory  tests  for  physicians  and  public 
health  agencies  throughout  the  northwestern  states.  These  duties,  how- 
ever, overlapped  with  other,  more  basic  studies,  such  as  identifying 
tick  vectors  of  diseases  and  studying  the  antigenic  relationships  among 
disease  organisms.  As  discussions  about  the  laboratory's  postwar  re- 
search program  continued,  NIH  administrators  moved  rapidly  to  trans- 
fer production  of  yellow  fever  and  rickettsial  vaccines  to  the  private 
sector.  The  last  batches  of  Spencer-Parker  vaccine  made  from  tick 
tissues  were  produced  in  1948.  The  chief  vaccine  maker,  Earl  Malone, 
who  had  supervised  production  since  the  mid  1920s,  turned  to  other 
assignments  until  his  retirement  in  1958.^^ 

In  January  1949  Victor  H.  Haas,  first  director  of  the  National  Mi- 
crobiological Institute,  traveled  to  Montana  to  discuss  with  Ralph  R. 
Parker  how  RML  should  redirect  its  research  in  light  of  the  new  NIH 
emphasis. The  ambiguity  of  the  Steelman  distinctions  between  basic 
and  applied  research  was  clearly  revealed  in  the  interchanges  between 
Haas  and  Parker  at  the  conference.  "It  is  especially  important,"  Haas 
stated  to  Parker, 

that  we  shall  conform  to  the  policy  decisions  made  by  higher  levels  that  the 
function  of  the  N.I.H.  is  basic  research.  ...  I  think  many  things  that  were 


2l8 


Rocky  Mountain  Spotted  Fever 


fundamental  research  a  year  ago  or  a  month  ago  or  lo  years  ago  are  not 
fundamental  research  today.  Let  us  say,  for  example,  that  when  the  natural 
history  of  spotted  fever  was  unknown,  investigation  of  that  problem  was 
fundamental  research,  just  as  I  think  the  investigation  of  equine  encephalo- 
myelitis is  fundamental  research  today. 

Parker  took  issue:  "I  would  disagree  that  we  know  the  natural  history 
of  spotted  fever— we  know  very  little  about  it."  Haas  replied,  "That 
is  right.  I  only  used  that  as  an  illustration."^^ 

Although  Parker  was  prepared  to  redirect  the  RML's  research  in 
accordance  with  NIH  policy,  he  was  never  able  to  implement  the  new 
plans.  On  4  September  1949  he  suffered  a  heart  attack  and  died.^^  In 
the  history  of  Rocky  Mountain  spotted  fever,  Parker's  death  may  be 
viewed  as  a  watershed.  He  had  investigated  the  ecology  of  spotted 
fever,  participated  in  the  development  of  the  tick  tissue  vaccine,  su- 
pervised the  production  of  the  Cox  vaccine,  personally  tested  the  ef- 
ficacy of  numerous  drugs,  and  witnessed  the  introduction  of  effective 
broad-spectrum  antibiotics.  Parker  probably  possessed  a  broader 
knowledge  of  spotted  fever  than  did  any  other  single  person.  After  his 
death  the  history  of  spotted  fever  became  less  directly  tied  to  western 
Montana  and  to  the  Rocky  Mountain  Laboratory,  although  that  fa- 
cility continued  to  serve  as  a  major  center  for  rickettsial  research. 

In  the  late  1940s  the  wartime  vocabulary  of  conquest,  triumph,  and 
victory  seemed  particularly  appropriate  to  describe  the  half-century 
struggle  to  prevent  and  cure  the  most  severe  rickettsial  disease  in  the 
western  hemisphere.  And  indeed,  in  1949  the  first  of  a  genre  of  "con- 
quest" articles  appeared.  It  was  the  first  Howard  Taylor  Ricketts  Award 
Lecture  at  the  University  of  Chicago.  The  speaker  was  Russell  M. 
Wilder,  then  on  the  staff  of  the  Mayo  Clinic,  who  had  assisted  Ricketts 
in  the  19 10  research  on  typhus  fever  that  took  his  Hfe.  Entitling  his 
lecture  "The  Rickettsial  Diseases:  Discovery  and  Conquest,"  Wilder 
proclaimed,  "This  discovery  of  a  cure  .  .  .  represents  the  final  chapter 
of  an  epic."^°  His  choice  of  the  word  final  may  have  been  premature, 
but  without  doubt  the  impact  of  antibiotics  was  of  epic  proportion. 
By  fulfilling  the  promise  of  medical  research,  these  "miracle  drugs" 
justified  the  persistent  faith  and  optimism  of  investigators  and  laymen 
alike. 


Chapter  Eleven 


Spotted  Fever 
after  Antibiotics 


Experience  has  shown  that  success  may  be  temporary  when  all  the  answers 
are  not  known. 

Mack  I.  Shanholtz,  Virginia  State  Health  Commissioner,  1961 


During  the  1950s,  Rocky  Mountain  spotted  fever  seemed  nearly  to 
disappear  in  the  United  States.  The  number  of  reported  cases  fell  from 
570  in  1949  to  301  in  1953.  Throughout  the  remainder  of  the  decade, 
the  incidence  of  the  disease  hovered  at  250—300  cases  with  fewer  than 
two  dozen  deaths  per  year/  Except  for  the  families  and  friends  of  the 
victims,  most  people  could  argue  with  conviction  that  antibiotics  and 
insecticides  had  eHminated  spotted  fever  as  a  threat  to  modern  society. 
Because  Rickettsia  rickettsii  had  not  been  eradicated,  however,  the 
history  of  Rocky  Mountain  spotted  fever  did  not  end  with  antibiotics. 
The  period  between  the  late  1940s  and  the  early  1970s  may  be  char- 
acterized as  a  time  of  little  drama  in  the  story,  yet  it  was  during  these 
years  that  much  of  the  morphology,  ecology,  and  physiology  of 
R.  rickettsii  was  elucidated. 

One  significant  portion  of  the  ecology  of  spotted  fever  was  defined 
between  1935  and  1950.  During  this  period  the  disease  was  shown 
to  be  widespread  throughout— and  apparently  exclusive  to— the  west- 
ern hemisphere.^  In  South  America  by  the  early  1940s  spotted  fever 
was  known  to  exist  in  Tobia,  Colombia,  and  in  rural  areas  of  Sao 
Paulo,  Minas  Gerais,  and  Rio  de  Janeiro,  Brazil.^  In  1938  the  first 
figures  on  spotted  fever  in  Canada  revealed  that,  although  the  disease 
had  been  known  since  1923,  only  eight  cases  were  officially  docu- 
mented."^  During  the  next  decade,  a  project  to  amass  data  on  spotted 
fever  and  bubonic  plague  in  Canada  revealed  that  cases  of  spotted 
fever  were  known  in  British  Columbia,  Alberta,  and  Saskatchewan, 
with  most  cases  occurring  in  southeastern  Alberta.  Three  species  of 
spotted  fever  tick  vectors  were  identified,  but  only  D.  andersoni,  abun- 


219 


220 


Rocky  Mountain  Spotted  Fever 


150  -| 


i«0  - 


q4  ^  ;  ^  ,  ,  4-0 

1940  I9';5  1950  1955  i960  1965  1970 


Deaths  and  ratios  of  cases  to  fatalities  of  Rocky  Mountain  spotted  fever  in 
the  United  States,  1940-70.  The  solid  line  represents  the  number  of  deaths; 
the  dotted  line  tracks  the  ratio  of  cases  to  fatalities— that  is,  the  mortality 
percentage.  The  data  for  1968  were  provisional.  The  impact  of  broad 
spectrum  antibiotics,  introduced  in  1948,  is  dramatically  apparent. 
(Reproduced  from  Michael  A.  W.  Hattwick,  "Rocky  Mountain  Spotted 
Fever  in  the  U.S.,  1920-1970,"  Journal  of  Infectious  Diseases  124  [1971]: 
112-14.) 

dant  in  the  southern  part  of  the  three  western  provinces,  was  known 
to  harbor  virulent  strains  of  R.  rickettsii.  The  small  number  of  infected 
ticks  in  nature  and  the  tedious  work  of  surveying  them  were  under- 
scored by  the  Canadian  report:  only  5  of  72,227  ticks  collected  in 
British  Columbia  and  only  10  of  49,201  collected  in  Alberta  were 
demonstrated  to  be  infective.^ 

For  some  time,  spotted  fever  seemed  curiously  absent  from  Mexico 
and  other  Central  American  countries.  Writing  in  1943,  Gordon  E. 
Davis  of  the  Rocky  Mountain  Laboratory  observed  that  it  hardly 
seemed  "credible  that  a  disease  present  in  southwestern  Canada, 


spotted  Fever  after  Antibiotics 


221 


throughout  the  United  States,  in  Colombia,  and  Brazil  should  be  en- 
tirely absent"  from  the  Central  American  region.^  Indeed,  the  following 
year  "an  acute  petechial  fever  with  a  high  death  rate,"  was  reported 
from  the  districts  of  Choix  and  Fuerte  de  Sinaloa  in  Mexico.  Local 
residents,  who  called  the  affliction  fiebre  de  Choix  or  fiebre  manchada^ 
reported  to  Miguel  E.  Bustamante  and  Gerardo  Varela  of  the  Instituto 
de  Salubridad  y  Enfermedades  Tropicales  in  Mexico  City  that  the 
affliction  appeared  each  year.  A  75  percent  mortality,  typical  rickettsial 
symptoms,  and  the  presence  of  ticks  strongly  suggested  Rocky  Moun- 
tain spotted  fever.^  Subsequent  studies  confirmed  that  spotted  fever 
existed  alongside  murine  typhus  in  the  Mexican  states  of  Durango  and 
Sinaloa,  and  that  it  occurred  with  epidemic  typhus  in  San  Luis  Potosi 
and  Veracruz.  All  three  rickettsial  diseases  occurred  in  Coahuila.  Only 
in  Sonora  did  spotted  fever  exist  in  isolation.  Arthropod  vectors  found 
naturally  infected  were  R.  sanguineus  in  the  north  and  northeast 
regions  and  A.  cajennense  on  the  east  Mexican  coast.^ 

In  1950  spotted  fever  was  first  reported  in  Panama.  Although  the 
diagnosis  of  the  first  Panamanian  case  was  made  upon  autopsy,  the 
next  two  reported  victims  were  treated  with  antibiotics  and  recovered. 
Carlos  Calero  and  Jose  M.  Nuiiez  of  the  Panama  Hospital  and  Santo 
Thomas  Hospital  in  Panama  and  Roberto  Silva-Goytia  of  the  Instituto 
de  Salubridad  y  Enfermedades  Tropicales  in  Mexico  City  found  that 
infections  occurred  in  both  rural  and  urban  settings  across  the  isthmus. 
By  1953,  Enid  C.  de  Rodaniche  at  Gorgas  Memorial  Hospital  had 
recovered  Rickettsia  rickettsii  from  naturally  infected  Amblyomma 
cajennense  ticks,  already  known  as  a  vector  of  spotted  fever  in  Co- 
lombia, Mexico,  and  Brazil.  Because  this  tick  was  abundant  and  at- 
tacked humans  "readily"  in  all  stages,  Rodaniche  wondered  why  clin- 
ical spotted  fever  had  not  been  encountered  across  the  isthmus  with 
greater  frequency  in  the  past.^ 

Since  spotted  fever  had  been  identified  in  North,  South,  and  Central 
America,  Mexican  investigators  Bustamante  and  Varela  proposed  that 
its  name  be  changed  to  American  spotted  fever  to  eliminate  its  mis- 
leading exclusive  association  with  the  Rocky  Mountain  area  of  North 
America.  A  BraziHan  investigator  argued  that  all  geographical  adjec- 
tives should  be  abandoned  and  the  disease  called  simply  spotted  fever. 
U.S.  investigators  W.  M.  Kelsey  and  G.  T.  Harrell  suggested  that  tick- 
borne  typhus  was  the  most  appropriate  scientific  designation.  None 
of  these  proposals,  however,  gained  widespread  support.  The  popular 
name  Rocky  Mountain  spotted  fever  simply  could  not  be  dislodged. 

Complacency  about  spotted  fever,  of  course,  was  abetted  by  a  pleth- 
ora of  popular  articles  that  emphasized  the  miraculous  properties  of 


222 


Rocky  Mountain  Spotted  Fever 


antibiotics  and  insecticides  in  controlling  infectious  diseases.  A  fed- 
erally funded  flea  control  project  begun  in  1945  demonstrated  beyond 
cavil  DDT's  power  against  the  vectors  of  murine  typhus.  In  nine  south- 
eastern states  and  in  Texas— where  92  percent  of  all  cases  of  murine 
typhus  occurred— DDT  dusting  produced  a  62  percent  decline  in  cases. 
"Barrier  spraying"  against  ticks  along  roadsides,  the  dusting  of  dogs 
with  DDT,  and  the  development  of  more  effective  tick  repellents  played 
a  similar  role  in  the  containment  of  spotted  fever.  Confidence  in  the 
efficacy  of  insecticides  ran  so  high,  in  fact,  that  some  scientists  joked 
that  these  chemicals  might  render  their  positions  obsolete. 

Control  of  rickettsial  diseases  with  chemical  pesticides,  however, 
lasted  for  less  than  two  decades.  By  the  1960s  irrefutable  evidence  had 
been  amassed  that  mosquitoes,  lice,  mites,  and  other  arthropod  vectors 
could  develop  resistance  to  insecticides.  In  Silent  Spring,  her  celebrated 
book  on  the  dangers  of  the  indiscriminate  use  of  such  chemicals,  Rachel 
Carson  recorded  the  declining  power  of  DDT  against  typhus  after  its 
initial  success  during  World  War  II. 

The  control  of  body  lice  in  Naples  was  one  of  the  earliest  and  most  publicized 
achievements  of  DDT.  During  the  next  few  years  its  success  in  Italy  was 
matched  by  the  successful  control  of  lice  affecting  some  two  million  people 
in  Japan  and  Korea  in  the  winter  of  1945-46.  Some  premonition  of  trouble 
ahead  might  have  been  gained  by  the  failure  to  control  a  typhus  epidemic  in 
Spain  in  1948.  Despite  this  failure  in  actual  practice,  encouraging  laboratory 
experiments  led  entomologists  to  believe  lice  were  unlikely  to  develop  resist- 
ance. Events  in  Korea  in  the  winter  of  1950-51  were  therefore  startling.  When 
DDT  powder  was  applied  to  a  group  of  Korean  soldiers  the  extraordinary 
result  was  an  actual  increase  in  the  infestation  of  lice.  When  lice  were  collected 
and  tested,  it  was  found  that  5  per  cent  DDT  powder  caused  no  increase  in 
their  natural  mortality.  Similar  results  among  lice  collected  from  vagrants  in 
Tokyo,  from  an  asylum  in  Itabashi,  and  from  refugee  camps  in  Syria,  Jordan, 
and  eastern  Egypt,  confirmed  the  ineffectiveness  of  DDT  for  the  control  of 
lice  and  typhus.  When  by  1957  the  list  of  countries  in  which  lice  had  become 
resistant  to  DDT  was  extended  to  include  Iran,  Turkey,  Ethiopia,  West  Africa, 
South  Africa,  Peru,  Chile,  France,  Yugoslavia,  Afghanistan,  Uganda,  Mexico, 
and  Tanganyika,  the  initial  triumph  in  Italy  seemed  dim  indeed. 

As  with  insecticides,  broad-spectrum  antibiotics  were  used  widely, 
even  indiscriminately,  during  the  1950s.  Among  those  investigators 
who  monitored  the  incidence  of  spotted  fever  during  this  decade,  it 
was  apparent  that  the  popular  drugs  masked  its  true  incidence  in  the 
United  States.  "It  is  probably  safe  to  say,"  wrote  the  authors  of  a  1955 
review  paper,  "that  a  relatively  small  percentage  of  Rocky  Mountain 
spotted  fever  and  typhus  infections  now  develop  to  the  point  of  com- 
plete diagnosis  and  reporting."  Further  complicating  the  picture  was 
the  influence  of  antibiotics  on  diagnostic  tests.  Studies  at  the  Rocky 


spotted  Fever  after  Antibiotics 


223 


Mountain  Laboratory  revealed  that  the  appearance  of  antibodies  in 
both  the  Weil-FeHx  and  the  complement  fixation  tests  was  altered  if 
the  patient  had  received  antibiotics.  It  also  became  increasingly  hard 
to  obtain  blood  samples  that  show^ed  a  change  in  antibody  level.  Pa- 
tients receiving  antibiotics  rarely  returned  to  their  physicians  for  a 
follow-up  blood  test.  It  thus  became  virtually  impossible  to  confirm 
suspected  cases. 

The  popularity  of  the  "miracle  drugs,"  moreover,  deflected  early 
reports  about  their  toxic  side  effects.  Chloramphenicol,  which  had 
passed  toxicity  tests  in  animals  and  appeared  to  have  no  adverse  effects 
other  than  causing  temporary  anemia,  was  in  wide  use  before  its 
dangers  came  to  pubhc  attention.  Evidence  gathered  as  early  as  1950 
that  the  drug  could  cause  a  dangerous  depression  of  the  blood  marrow 
resulting  in  fatal  aplastic  anemia  at  first  attracted  little  attention.  Be- 
cause death  often  occurred  two  or  more  months  after  treatment  had 
stopped,  it  was  often  difficult  to  relate  it  to  the  earher  administration 
of  chloramphenicol.  In  1952,  however,  accounts  of  an  entire  series  of 
such  cases  temporarily  restricted  the  use  of  the  drug.  Soothing  phar- 
maceutical propaganda,  however,  soon  restored  the  use  of  chloram- 
phenicol to  a  high  level.  Further  evidence  of  the  drug's  hazards  ap- 
peared some  years  later,  when  it  was  often  administered  to  newborn 
babies  prophylactically.  Many  of  these  infants  developed  the  so-called 
grey  syndrome,  named  for  the  ashen  grey  pallor  that  accompanied 
circulatory  collapse  and  death.  It  was  not  until  1959,  however,  that 
a  therapeutic  experiment  at  the  Los  Angeles  County  Hospital  dem- 
onstrated chloramphenicol's  causative  connection  to  this  condition. 

By  the  early  1960s  medical  texts  began  recommending  against  the 
use  of  chloramphenicol  for  rickettsial  infections,  usually  noting  the 
tetracyclines  as  effective  alternatives.  Even  as  these  texts  came  off  the 
presses,  additional  reports  appeared,  suggesting  that  the  tetracyclines 
might  also  be  hazardous,  especially  to  patients'  teeth.  Since  1957  the 
tetracyclines  had  been  known  to  have  an  affinity  for  bone  tissue. 
Because  the  drugs  fluoresced  under  ultraviolet  light,  scientists  could 
identify  the  sites  in  the  body  where  they  lodged  after  treatment.  In 
1962,  I.  S.  Walton  and  H.  B.  Hilton  at  the  King  Edw^ard  Memorial 
Hospital  for  Women  in  Perth,  Australia,  published  the  results  of  a 
study  on  fifty  babies  who  had  received  the  drugs  during  their  first  few 
weeks  of  life.  Forty-six  of  the  children  suffered  stains  on  their  primary 
teeth.  As  with  those  children  treated  with  chloramphenicol,  nearly  half 
of  these  babies  had  been  given  tetracyclines  prophylactically  rather 
than  for  any  medical  problem.  In  1963  investigators  at  the  National 
Institute  of  Dental  Research  pubUshed  a  review  article  alerting  the 


224 


Rocky  Mountain  Spotted  Fever 


medical  community  to  the  dangers  of  these  drugs.  "TetracycHne  is  the 
drug  of  choice  in  many  infections  in  which  the  consequences  of  the 
infection  outweigh  the  possible  damage  to  the  teeth,"  they  concluded, 
but  they  warned  about  the  hazards  of  injudicious  use.^^ 

With  a  death  rate  of  over  20  percent  in  untreated  persons.  Rocky 
Mountain  spotted  fever  was  one  of  those  diseases  in  which  the  risks 
of  the  tetracyclines  or  even  chloramphenicol  seemed  worth  taking. 
When  the  1950s  enthusiasm  for  antibiotics  gave  way  by  the  1970s  to 
extreme  caution  in  prescribing  such  drugs,  those  physicians  who  fre- 
quently treated  spotted  fever  cases  had  no  hesitation  about  their  use. 
Thus  a  1977  paper  in  the  Journal  of  the  American  Medical  Association 
suggesting  that  the  tetracyclines  should  be  virtually  abandoned  drew 
sharp  criticism  from  southeastern  physicians  located  in  endemic  spot- 
ted fever  areas.  Noting  that  a  single,  short  course  of  oxytetracycline 
or  doxycycline  caused  the  least  staining  of  teeth,  they  were  clearly 
willing  to  subject  their  patients  to  the  risk  of  a  nonfatal  condition  in 
order  to  save  them  from  potentially  fatal  spotted  fever. 

Antibiotics  proved  to  be  double-edged  swords,  but  their  advent  at 
the  end  of  World  War  II  had  signaled  a  decline  in  concern  about  many 
infectious  diseases,  especially  those,  such  as  Rocky  Mountain  spotted 
fever,  that  struck  so  few  victims  each  year.  To  be  sure,  people  continued 
to  die  from  spotted  fever  as  well  as  from  other  infectious  diseases,  but 
the  American  animus  against  death  was  largely  redirected  after  World 
War  II  toward  the  chronic  diseases,  especially  cancer  and  heart  disease, 
which  had  been  growing  as  foci  of  public  concern  since  the  1920s.  As 
a  result,  the  1950s  witnessed  a  dramatic  plunge  in  federal  funding  for 
research  on  infectious  diseases  relative  to  the  rising  rate  for  research 
on  chronic  diseases.  In  a  1957  study,  for  example,  Charles  V.  Kidd 
observed  that  between  1948  and  1954  the  study  of  communicable 
diseases  had  dropped  from  first  to  eighth  place  in  terms  of  federal  and 
foundation  monies  allocated  for  their  support.  Studies  of  the  endocrine 
system,  in  contrast,  had  risen  from  fifteenth  to  fourth.  Although  Kidd 
noted  that  such  classifications  of  research  might  be  somewhat  arbitrary 
and  at  times  influenced  by  fads,  he  concluded  that  the  figures  confirmed 
"the  general  opinion  that  the  substance  of  medical  research"  had 
"indeed  shifted  remarkably  over  the  last  decade." 

In  spite  of  the  facts  that  more  patients  visited  physicians  because  of 
infections  than  for  any  other  group  of  illnesses  and  that  infections  in 
the  United  States  were  the  primary  cause  of  death  in  6  percent  of  all 
deaths,  investigators  found  funding  agencies,  whether  Congress  or 
private  foundations,  more  inclined  to  support  research  on  chronic 
diseases.  Dorland  J.  Davis,  director  of  the  National  Institute  of  Allergy 


spotted  Fever  after  Antibiotics 


225 


and  Infectious  Diseases  from  1964  to  1975,  articulated  the  often  un- 
thinking assumptions  that  plagued  infectious  disease  research.  "I  recall 
becoming  terribly  annoyed  at  a  chart  that  was  proposed  for  showing 
to  some  influential  group— I  don't  know  whether  it  was  Congress  or 
another  group— which  showed  the  death  rates  for  cancer  and  heart 
disease  going  up  steeply  and  the  death  rate  for  infectious  disease  going 
down  sharply.  I  think  I  got  it  stopped  all  right,  but  ...  it  took  quite 
an  effort  to  get  people  to  think  of  infectious  diseases  as  still  a  serious 
health  problem.''^^ 

The  National  Institute  of  Allergy  and  Infectious  Diseases  was  the 
categorical  incarnation  of  the  former  National  Microbiological  Insti- 
tute. One  story,  probably  apocryphal  but  nonetheless  revealing,  held 
that  the  new  name  enhanced  Congress's  willingness  to  grant  the  in- 
stitute funds  because  people  continued  to  die  of  infectious  diseases  and 
suffer  from  allergies,  but  "nobody  ever  died  of  microbiology."^^  Despite 
the  new  name,  a  1965  analysis  of  federal  support  for  research  in 
microbiology  found  that  the  field  remained  significantly  undersup- 
ported.  Prepared  for  President  Lyndon  Johnson  as  a  part  of  a  larger 
review  of  the  NIH,  and  popularly  known  as  the  Wooldridge  Committee 
report,  the  study  attributed  the  situation  to  several  factors,  including 
the  perception  that  antibiotics  had  solved  the  problem  of  infectious 
diseases.  Another,  more  difficult  problem  to  attack  was  the  overshad- 
owing of  traditional  microbiological  research  by  the  "glamour  and 
scientific  status  of  the  flowering  field  of  molecular  biology."  Although 
agreeing  that  this  new  field  was  undeniably  important,  the  review  panel 
believed  that  its  attraction  had  retarded  more  traditional  studies  of 
"host-parasite  relationships,"  the  whole  field  of  tropical  medicine,  and 
medical  entomology.^^ 

For  rickettsial  diseases  in  particular,  major  federal  funding  was  pro- 
vided by  two  agencies.  The  smaller  of  the  two  was  the  Commission 
on  Rickettsial  Diseases  of  the  Armed  Forces  Epidemiological  Board, 
one  of  several  commissions  supported  by  the  board  to  maintain  ex- 
pertise in  particular  diseases  of  military  importance,  especially  in  the 
event  of  atomic  warfare.  "Despite  its  name,"  wrote  Paul  B.  Beeson, 
the  board  was  "primarily  a  civilian  agency."  Its  Commission  on  Rick- 
ettsial Diseases,  headed  first  by  Joseph  E.  Smadel  and  subsequently  by 
Charles  L.  Wisseman,  Jr.,  supported  university  research  on  rickettsiae 
through  three  or  four  U.S.  Army  or  U.S.  Navy  contracts  each  year, 
ranging  from  $30,000  to  $250,000.  According  to  Wisseman,  during 
the  1960s  these  contracts  resembled  grant  awards  in  support  of  re- 
spected research  programs  rather  than  the  more  usual  military  mech- 
anism of  quid  pro  quo  service  contracts.  Meetings  of  the  commission, 


226 


Rocky  Mountain  Spotted  Fever 


furthermore,  provided  a  scientific  forum  for  U.S.  rickettsiologists  and 
a  national  meeting  at  which  promising  young  investigators  could  be 
recruited. 

The  second  source  of  federal  funds  for  rickettsial  research  was  the 
grants  program  of  the  National  Institutes  of  Health,  especially  the 
National  Microbiological  Institute  and  its  successor  institute,  the  Na- 
tional Institute  of  Allergy  and  Infectious  Diseases.  Between  1946,  when 
the  grants  mechanism  began  to  function,  and  1971,  when  the  situation 
began  to  change  somewhat,  slightly  less  than  $6  million  in  grants  was 
awarded  for  research  on  rickettsial  diseases  compared  to  more  than 
$526  milhon  awarded  by  the  National  Microbiological  Institute  and 
NIAID  for  all  types  of  extramural  research  in  microbiology,  parasi- 
tology, virology,  and  immunology.^'*  This  relatively  low  level  of  funding 
was  due  in  part  to  the  small  number  of  new  researchers  coming  into 
the  field  of  rickettsiology  and  in  part  to  a  growing  emphasis  on  viral 
and  immunological  research.  New  techniques  made  virology  and  im- 
munology fruitful  fields,  and  many  of  the  diseases  caused  by  viruses 
and  immunological  deficiencies  had  no  known  treatment. 

Those  young  investigators  who  did  enter  the  field  of  rickettsiology 
generally  came  from  a  relatively  small  number  of  institutions  whose 
interest  in  rickettsial  diseases  was  historic  or  had  developed  during 
World  War  II.  Initially  most  rickettsial  investigators  were  housed  at 
the  National  Institutes  of  Health,  with  rickettsial  units  at  Bethesda, 
Maryland,  and  at  the  Rocky  Mountain  Laboratory  in  Hamilton,  Mon- 
tana; at  the  military  viral  and  rickettsial  unit  at  Walter  Reed  Army 
Institute  for  Research  in  Washington,  D.C;  and  at  Harvard  University 
Medical  School  in  Cambridge,  Massachusetts,  site  of  the  investigations 
of  S.  Burt  Wolbach  and  Hans  Zinsser.  The  University  of  Chicago, 
home  of  Howard  Taylor  Ricketts,  also  fostered  some  rickettsial  re- 
search, as  did  the  Rockefeller  Institute  for  Medical  Research  in  New 
York,  the  locale  of  Hideyo  Noguchi's  early  work.  Investigators  trained 
in  these  centers  had  also  established  satellite  programs  in  several  uni- 
versities. Henry  Pinkerton,  for  example,  studied  with  Wolbach  at  Har- 
vard and  later  moved  to  Saint  Louis  University  School  of  Medicine. 
One  center  of  clinical  research  on  Rocky  Mountain  spotted  fever  grew 
up  in  North  Carolina,  a  site  of  high  spotted  fever  incidence  in  the  east. 
Another  became  established  at  the  University  of  Maryland  School  of 
Medicine  in  Baltimore,  largely  as  a  result  of  collaboration  with  the 
unit  at  Walter  Reed  in  Washington,  D.C.  Once  Q  fever  had  been 
identified  as  a  major  problem  across  the  western  states,  several  western 
universities  and  public  health  agencies,  especially  in  Texas,  Kansas, 
and  California,  developed  expertise  in  this  rickettsial  disease.  Most  of 


spotted  Fever  after  Antibiotics 


227 


the  rickettsial  investigators  who  directed  these  programs  during  the 
1950s  had  been  trained,  of  course,  in  the  crucible  of  wartime  work 
with  the  U.S.A.  Typhus  Commission." 

NIH  grants  for  rickettsial  diseases  were  inaugurated  in  1946,  with 
a  $7,240  grant  to  J.  A.  Montoya  of  the  Pan  American  Sanitary  Bureau 
for  an  immunological  comparison  of  the  Cox  and  Castaneda  typhus 
vaccines.  Throughout  the  1950s  and  1960s,  investigators  were  funded 
for  studies  of  rickettsial  epidemiology,  for  research  on  immunology 
and  serological  tests,  for  the  maintenance  of  rickettsiae  in  cell  Hnes, 
and  for  the  investigation  of  arthropod  vectors. This  work  was  com- 
plemented by  the  intramural  NIAID  rickettsial  diseases  program,  lo- 
cated at  the  RML.  With  its  ever-growing  collection  of  ticks  from  around 
the  world,  the  RML  became  an  official  tick  reference  center  for  the 
World  Health  Organization. 

Basic  laboratory  research  on  rickettsiae  also  prospered.  With  tech- 
nical advances  pioneered  during  the  1930s  and  1940s,  investigators 
were  able  to  define  the  morphology  and  physiology  of  rickettsiae  more 
precisely.  One  of  the  most  dramatic  new  instruments  of  the  early  1940s 
was  the  electron  microscope,  which  permitted  scientists  to  go  beyond 
their  limitations  under  light  microscopes  in  understanding  the  structure 
of  tiny  microorganisms.^^  "It  is  a  well  recognized  principle  in  natural 
science  that  understanding  of  structure  is  basic  to  analysis  of  function," 
wrote  Stuart  Mudd  and  Thomas  F.  Anderson  of  the  University  of 
Pennsylvania  in  a  paper  on  the  impHcations  of  electron  microscopy. 
With  the  light  microscope,  researchers  had  not  been  able  to  resolve 
the  fine  structure  of  bacterial  cells  or  rickettsiae,  nor  could  they  visualize 
at  all  most  of  the  viruses.  "Bacteria  and  rickettsias  as  examined  by 
ordinary  bacteriologic  methods  appear  to  be  simple  and  structureless," 
Mudd  observed  in  a  companion  paper,  and  he  cautioned,  "The  long 
habit  of  observing  such  minute  and  apparently  simple  objects  is  often 
reflected  in  methods  of  dealing  with  bacteria  in  practice  as  though  they 
were  much  simpler  than  they  actually  are."^^ 

The  electron  microscope  provided  the  first  clues  to  the  complex 
structure  of  rickettsiae,  which  generally  had  been  grouped  with  the 
viruses  because  of  their  common  requirement  of  intracellular  existence. 
In  1943,  Harry  Plotz  and  his  colleagues  published  the  first  electron 
micrographs  of  rickettsiae  in  the  Journal  of  Experimental  Medicine. 
Comparing  the  organisms  of  epidemic  and  murine  typhus,  Rocky 
Mountain  spotted  fever,  and  Q  fever,  they  found  striking  similarity  in 
the  morphological  structure  of  the  four  types  of  organisms.  The  new 
instrument  clearly  showed  that  rickettsiae,  Hke  bacteria,  had  a  limiting 
cell  wall  distinct  from  the  inner  protoplasm. 


228 


Rocky  Mountain  Spotted  Fever 


Furthermore,  the  electron  microscope  not  only  revealed  the  larger 
rickettsial  forms  previously  studied  with  the  light  microscope  but  also 
rendered  visible  "smaller  coccoidal  forms  of  rickettsiae"  identified  by 
their  limiting  membrane  and  internal  structure.  These  small  oval  forms 
were  of  considerable  interest,  Plotz  and  his  associates  stated,  because 
they  could  not  be  differentiated  with  certainty  from  tissue  particles  by 
ordinary  microscopy.  "The  occurrence  of  such  organisms  may  throw 
light  on  the  concept  of  'invisible  forms'  of  rickettsiae  which  has  been 
brought  forward  to  explain  certain  experiments  in  which  rickettsiae 
have  not  been  demonstrated  in  material  of  known  infectivity."  The 
detection  of  rickettsiae  invisible  under  ordinary  methods  apparently 
elucidated  one  of  the  mysteries  that  had  hindered  acceptance  of  the 
organisms  as  the  etiological  agents  of  the  typhus-like  diseases.  Both 
Roscoe  R.  Spencer  and  Ralph  R.  Parker  must  have  welcomed  the 
vindication  of  their  findings.  In  the  margin  of  one  copy  of  their  initial 
paper  reporting  the  existence  of  apparently  invisible  forms  of  rickett- 
siae, one  anonymous  skeptic  had  written,  "Can't  see  it,  can't  measure 
it— it  doesn't  exist."^° 

Stuart  Mudd's  prophecy  that  knowledge  about  the  structure  of  or- 
ganisms would  enhance  understanding  of  their  function  was  soon 
reahzed  in  the  case  of  the  rickettsiae.  "Since  electron  microscopy  shows 
that  the  cell  walls  of  bacteria  and  rickettsias  form  a  relatively  small 
fraction  of  the  mass  of  the  cells  and  since  the  inner  protoplasm  may 
be  toxic,  these  facts  have  practical  implications,"  he  observed.  "It  is 
perhaps  not  too  rash  to  predict  that  purified  surface  antigens  will 
increasingly  come  into  use  as  diagnostic  reagents  and  even  as  vaccines 
for  active  immunization."^^  Because  there  was  little  impetus  to  produce 
improved  rickettsial  vaccines  during  the  1950s  and  1960s,  however, 
the  use  of  purified  surface  antigens— the  proteins  on  the  outer  cell 
membrane  — as  laboratory  reagents  was  the  most  immediate  outcome 
of  the  new  knowledge. 

One  fruitful  line  of  research,  for  example,  was  the  more  specific 
characterization  of  rickettsiae.  Since  19 16  the  Weil-Felix  test  had  pro- 
vided a  means  for  crude  distinctions  among  members  of  the  typhus- 
like disease  group,  after  which  cross-protection  tests  in  guinea  pigs 
were  employed  for  more  precise  differentiation.  In  the  1930s  bouton- 
neuse  fever  had  been  distinguished  from  Rocky  Mountain  spotted  fever 
in  this  way.  More  sensitive  techniques  such  as  the  complement  fixation 
test,  which  had  been  made  possible  by  purified  surface  antigens,  soon 
thereafter  revealed  that  a  close  immunological  relationship  existed 
among  the  rickettsial  diseases. 


spotted  Fever  after  Antibiotics 


229 


Information  gleaned  in  such  studies  eventually  generated  a  new 
classification  system  that  replaced  the  earlier  schemes  based  on  place 
names,  geography,  or  vectors.  Regarding  the  awkwardness  of  these 
systems,  two  South  African  investigators,  Adrianus  Pijper  and  C.  G. 
Crocker  had  observed  in  1938:  "A  wit  once  divided  botanical  scientists 
into  two  classes,  the  lumpers  and  the  splitters.  In  1920  the  number  of 
Rickettsioses  for  which  a  separate  entity  was  claimed  was  three  or 
four,  and  in  1936  the  number  had  risen  to  well  over  twenty.  Has  there 
been  too  much  splitting,  and  is  lumping  indicated ?"^^ 

Complement  fixation  studies  permitted  rickettsial  diseases  to  be 
lumped  into  discrete  groups  displaying  similar  antigenic  properties: 
the  typhus  group,  the  tsutsugamushi  group,  and  the  spotted  fever 
group.  The  organisms  that  caused  Q  fever  and  trench  fever  proved  so 
antigenically  different  that  each  was  classified  in  a  wholly  separate 
genus.  Within  the  rickettsial  genus,  the  spotted  fever  group  was  dis- 
tinguished by  a  soluble  antigen  that  was  group  specific  and  fixed 
complement  in  the  presence  of  antibodies  induced  by  any  other  member 
of  the  group.  On  this  basis  the  group  included  all  the  tick-borne 
rickettsial  diseases  but  also  rickettsialpox,  which  had  a  mite  as  its 
vector.  Once  the  soluble  antigen  had  been  removed  from  a  specific 
culture  of  rickettsia  by  repeated  washings,  the  species-specific  antigens 
could  be  detected. 

This  technique  also  demonstrated  that  several  rickettsiae  isolated 
from  ticks  but  apparently  nonpathogenic  for  humans  belonged  in  the 
spotted  fever  group.  The  earliest  of  these  "organisms  in  search  of  a 
disease,"  as  they  were  sometimes  called,  was  named  Maculatum  agent 
in  1939  by  Ralph  R.  Parker,  when  he  and  his  colleagues  first  isolated 
it  in  Amblyomma  maculatum  ticks. In  1965  this  organism  was  re- 
named Rickettsia  parkeri  in  honor  of  Parker.^^  Two  other  nonpath- 
ogenic rickettsiae  were  identified  as  members  of  the  spotted  fever 
group:  Rickettsia  montana  and  the  Western  Montana  U  strain  of 
Rickettsia  rickettsii?^ 

Comparative  studies  between  Rickettsia  rickettsii  and  other  path- 
ogenic spotted  fever  group  rickettsiae  around  the  world  revealed  sur- 
prising relationships.  The  only  one  that  closely  resembled  Rickettsia 
rickettsii  was  Rickettsia  sibirica,  the  agent  of  North  Asian  tick  typhus, 
a  disease  first  described  in  the  1930s  and  found  throughout  Siberia  in 
the  Soviet  Union,  in  some  localities  of  China,  and  in  the  MongoHan 
Peoples  Republic.^^  Another  member  of  the  spotted  fever  group,  Rick- 
ettsia australis,  caused  a  disease  known  as  Queensland  tick  typhus, 
which  was  first  described  in  1946  in  North  Queensland,  Australia. 


230 


Rocky  Mountain  Spotted  Fever 


This  organism  responded  immunologically  like  Rickettsia  akari,  the 
agent  of  rickettsialpox.^^ 

In  1965,  David  B.  Lackman,  E.  John  Bell,  Herbert  G.  Stoenner,  and 
Edgar  G.  Pickens  at  the  Rocky  Mountain  Laboratory  proposed  that 
the  spotted  fever  group  organisms  be  divided  into  four  subgroups: 

A— Rickettsia  rickettsii,  and  Rickettsia  sibirica 

B— Rickettsia  conorii  and  Rickettsia  parkeri 

C— Rickettsia  akari  and  Rickettsia  australis 

T>  — Rickettsia  montana  and  Western  Montana  U  rickettsia'^'^ 

More  recent  studies,  hov^ever,  based  on  comparative  analyses  of  the 
genetic  composition  of  rickettsial  organisms,  suggest  that  some  tax- 
onomic  modifications  may  be  necessary.  R.  sibirica  may  be  sufficiently 
different  from  other  spotted  fever  group  organisms  to  occupy  a  separate 
category,  and  the  genomes  of  R.  rickettsii  and  R.  conorii  appear  to 
be  more  closely  related  than  previously  believed."^^ 

This  line  of  research  has  also  revealed  the  existence  of  other  rick- 
ettsial organisms,  whose  properties  have  not  been  explored  completely. 
In  India,  a  number  of  reports  between  1943  and  198 1  identified  variant 
spotted  fever  group  rickettsiae  as  causes  of  Indian  tick  typhus. Be- 
cause of  this  disease's  mild  clinical  manifestations,  however,  most  cases 
go  unreported,  and  additional  research  is  needed  for  more  accurate 
identification  of  the  specific  rickettsiae  involved.  In  1985  a  possibly 
new,  clearly  pathogenic  rickettsia  of  the  spotted  fever  group  was  iden- 
tified in  Japan  when  it  caused  three  cases  of  exanthemous  fever  in 
women  from  a  farm  area  in  Anan-shi.  Laboratory  study  ruled  out 
tsutsugamushi  and  confirmed  instead  an  infection  of  the  spotted  fever 
group."^^  Variant  spotted  fever  group  rickettsiae  have  also  been  de- 
scribed in  Israel,  in  Southeast  Asia,  and  in  Czechoslovakia. "^"^  They 
may  also  exist  in  Africa,  but,  as  in  India,  because  most  cases  go  unre- 
ported, information  is  more  difficult  to  gather."^^  New  nonpathogenic 
spotted  fever  group  rickettsiae  also  continue  to  be  identified,  including 
one  in  Switzerland  and  another  in  the  southeast  United  States."^^ 

By  the  late  1960s  another  body  of  work  that  utilized  new  instruments 
and  techniques  had  resolved  the  ambivalent  characterization  of  rick- 
ettsiae as  organisms  midway  between  bacteria  and  viruses.  Within  ten 
years  after  Wendell  Stanley  crystallized  the  tobacco  mosaic  virus  in 
1935,  other  scientists  had  discovered  that  viruses  were  not,  as  Stanley 
had  originally  beheved,  "autocatalytic  proteins."  Nucleic  acids  — de- 
oxyribonucleic acid  (DNA)  and  ribonucleic  acid  (RNA)— were  iden- 
tified as  the  components  of  cells  that  governed  life  processes,  not  only 


spotted  Fever  after  Antibiotics 


231 


of  viruses  but  of  all  living  things.  Bacteria  contained  DNA  in  their 
nuclei  and  RNA  in  their  cytoplasm.  Viruses  were  show^n  to  contain 
either  DNA  or  RNA  but  not  both.  Although  initial  research  on  rick- 
ettsiae  had  not  detected  RNA  in  these  organisms,  Hans  Ris  and  John 
P.  Fox  at  the  Rockefeller  Institute  demonstrated  in  1949  that  washing 
procedures  used  to  purify  rickettsiae  in  the  early  studies  had  destroyed 
or  greatly  reduced  the  RNA  in  rickettsial  cells.  Including  electron 
micrographs  showing  distinct  nuclear  structures  in  rickettsiae,  they 
reported  that  both  DNA  and  RNA  were  indeed  present  in  these  or- 
ganisms. 

Further  buttressing  this  position  was  a  1949  study  by  Marianna  R. 
Bovarnick  and  her  mentor  John  C.  Snyder  at  Harvard  University  that 
demonstrated  independent  metabolic  activity  in  rickettsiae  — a  char- 
acteristic not  shared  by  viruses.  Using  the  Warburg  respirometer,  a 
device  developed  in  the  1920s  by  Nobel  prize  winner  Otto  Warburg 
for  measuring  metabolic  activity,  Bovarnick  and  Snyder  established 
that  purified  suspensions  of  epidemic  and  murine  typhus  rickettsiae 
exhibited  a  distinctive  respiratory  activity,  glutamate  oxidation.  Their 
work  provided  the  impetus  to  other  workers,  who  further  clarified  the 
process  of  rickettsial  metabolism  and  verified  that  rickettsiae,  unlike 
viruses,  were  also  able  to  perform  some  reactions  necessary  for  their 
own  proliferation.^^ 

Improved  tissue  culture  methods  in  the  1950s  also  enhanced  studies 
on  the  morphology  and  physiology  of  rickettsiae  under  controlled 
conditions.  The  mechanism  by  which  rickettsiae  invaded  cells  was 
studied  by  Zanvil  A.  Cohn  and  his  colleagues  at  Walter  Reed  Army 
Institute  of  Research.  They  concluded  that  rickettsiae  attacked  only 
living  cells  and  described  conditions  necessary  for  entry  to  occur.  Build- 
ing on  Cohn's  work,  Herbert  H.  Winkler  and  EUzabeth  T.  Miller  of 
the  University  of  South  Alabama  College  of  Medicine  later  observed 
that  an  organism  attaches  itself  to  a  host  cell  membrane  and  "tickles" 
the  cell  to  induce  phagocytosis,  the  process  of  being  taken  into  a  cell. 
Once  inside  the  host  cell,  rickettsiae  grow  and  multiply  with  little 
detectable  damage  to  the  parasitized  cell  until  it  finally  ruptures.^^ 

The  Walter  Reed  rickettsial  team  showed  that  single  cells  of  Rick- 
ettsia rickettsii  divided  by  transverse  binary  fission,  a  bacterial  but  not 
viral  phenomenon.  In  the  course  of  their  work,  they  had  also  noted 
that  the  spotted  fever  organism  sometimes  emerged  from  infected  cells 
"by  way  of  long,  filamentous  microfibrillar  structures  protruding  from 
the  edge  or  surface  of  the  cell."  Although  the  number  of  rickettsiae 
lost  from  cells  via  microfibrils  was  small,  they  believed  that  this  mech- 


232 


Rocky  Mountain  Spotted  Fever 


anism  deserved  "careful  consideration"  since  it  might  "play  an  im- 
portant role  in  dissemination  of  pathogens,  particularly  between  ad- 
jacent cells."^^ 

By  1969  the  body  of  knowledge  so  carefully  built  in  these  studies 
led  to  the  overwhelming  conclusion  that  rickettsiae  were  not  akin  to 
viruses  but  were  instead  "highly  fastidious  bacteria,"  as  Richard  A. 
Ormsbee,  a  specialist  in  Q  fever  rickettsiae  at  the  Rocky  Mountain 
Laboratory,  described  them  in  a  review  paper.  "The  importance  of 
this  conceptual  advance"  could  not  be  "stressed  too  strongly,"  Charles 
L.  Wisseman,  Jr.,  of  the  University  of  Maryland  School  of  Medicine 
observed  some  years  later,  because  "it  brought  to  bear  on  rickettsiology 
the  enormous  conceptual  framework  of  the  science  of  bacteriology." 
During  the  1970s  and  1980s,  moreover,  rapid  strides  in  technology 
unshackled  the  study  of  rickettsiae  in  the  laboratory.  Improved  puri- 
fication methods,  simple  methods  for  counting  the  organisms,  and 
better  methods  for  cloning  rickettsiae  were  among  the  many  new 
techniques  available. 

Unfortunately,  even  as  these  new  techniques  were  being  developed, 
it  appeared  that  research  interest  in  rickettsiae  and  rickettsial  diseases 
would  not  be  sustained  in  the  United  States.  Throughout  the  1950s 
and  1960s  the  numbers  of  rickettsial  investigators  had  declined  stead- 
ily.^^  By  1967  they  had  become  so  scarce  in  the  United  States  that, 
one  scientist  observed,  they  had  "trouble  having  a  meeting  other  than 
dinner  together."^^  In  1971,  moreover,  the  number  of  NIH  grants  for 
rickettsial  disease  research  reached  a  nadir  of  between  two  and  five, 
depending  on  how  one  counted  related  subjects. This  problem  often 
became  the  focus  of  discussions  at  meetings  of  the  Commission  on 
Rickettsial  Diseases,  and  two  participants  in  these  deliberations  sum- 
marized the  situation  in  published  articles.  Theodore  E.  Woodward  of 
the  University  of  Maryland  School  of  Medicine  lamented  the  lack  of 
young  people  attracted  to  the  field,  observing  that  those  researchers 
who  still  thought  about  rickettsiae  almost  every  day  had  "a  generous 
display  of  gray  hair."  Richard  A.  Ormsbee  cited  figures  showing  that 
when  grouped  by  age,  the  largest  group  of  rickettsial  researchers  av- 
eraged 55  years  old;  the  next  largest  group,  65  years  of  age.  "Only 
four  scientists  under  40  years  of  age  were  in  career  jobs  as  rickett- 
siologists  in  1971."^^ 

The  preservation  of  rickettsiology  as  a  separate  field  of  inquiry  was 
further  jeopardized  when  the  military  services  began  reevaluating  their 
programs  in  this  area.  In  1973  the  Armed  Forces  Epidemiological  Board 
disbanded  all  its  commissions,  including  the  Commission  on  Rickettsial 
Diseases.  Because  this  organization  had  served  as  the  major  national 


spotted  Fever  after  Antibiotics 


233 


forum  for  rickettsiologists,  its  demise  came  as  a  blow  to  many  in  the 
field.  The  U.S.  Army,  moreover,  shifted  its  research  priorities  away 
from  rickettsial  diseases  in  general  to  focus  on  developing  a  vaccine 
against  scrub  typhus,  because  of  that  disease's  potential  military  im- 
portance. Likewise,  U.S.  Navy  research  emphasis  was  directed  toward 
preparing  new  vaccines  against  murine  and  epidemic  typhus.  This  left 
the  National  Institute  of  Allergy  and  Infectious  Diseases  in  the  "awk- 
ward spot,"  as  its  deputy  director,  John  R.  Seal,  later  noted,  "of  being 
the  principal  Government  supporter  of  rickettsial  research  but  not 
having  been  given  any  extra  funds  to  meet  this  responsibility."^^ 

At  NIAID,  furthermore,  the  historic  debate  over  the  inclusion  of 
medical  entomology  in  the  research  program  had  been  revived  in  the 
late  1960s  when  U.S.  involvement  in  the  Vietnam  War  led  to  tighter 
budgets  for  medical  research.  Institute  administrators  and  the  Board 
of  Scientific  Counselors,  an  advisory  group  of  distinguished  nongov- 
ernmental scientists,  intensively  examined  existing  programs  as  they 
struggled  with  questions  of  research  priorities  in  a  period  of  restricted 
growth.  The  merit  of  traditional  epidemiological  and  microbiological 
studies  of  vector-borne  diseases  also  came  under  scrutiny  during  this 
period.  Because  intramural  rickettsial  and  entomological  research 
sponsored  by  NIAID  was  located  at  the  Rocky  Mountain  Laboratory, 
the  future  of  this  facility  became  the  focus  of  debate. 

Those  who  believed  that  research  in  medical  entomology  should  be 
abandoned  argued  that  it  was  more  properly  supported  by  the  military 
or  by  the  National  Science  Foundation.  In  addition,  they  believed  that 
if  the  institute  sought  to  maintain  leadership  in  medical  research,  it 
should  support  promising  studies  in  immunology  and  in  molecular 
biology  more  substantially  than  traditional  microbiological  and  epi- 
demiological research.  Supporters  of  the  opposing  position  argued  that 
medical  entomologists  afforded  expertise  nowhere  else  available  to 
physicians  around  the  world  who  needed  aid  in  identifying  vectors  of 
unknown  diseases.  Time  and  again,  the  U.S.  experience  with  scrub 
typhus  during  World  War  II  was  cited  as  an  example  of  the  kind  of 
unknown  arthropod-borne  diseases  that  the  country  might  encounter 
if  drawn  into  a  war  in  tropical  regions.^' 

By  the  late  1970s  tight  budgets  and  staff  reductions  impelled  NIAID 
administrators  to  revise  institute  priorities  for  the  intramural  program. 
At  the  end  of  the  decade,  medical  entomology  was  discontinued  at  the 
Rocky  Mountain  Laboratory  and  the  historic  tick  collection  shipped 
to  the  Smithsonian  Institution.  The  RML  was  reorganized  into  three 
laboratories,  only  one  of  which  continued  the  traditional  research 
program,  and  the  facility  was  renamed  the  Rocky  Mountain  Labo- 


234 


Rocky  Mountain  Spotted  Fever 


ratories.  Under  the  auspices  of  the  NIAID  extramural  program,  how- 
ever, a  variety  of  grants  and  contracts  for  rickettsial  disease  research 
continued  to  be  funded,  and,  indeed,  virtually  all  university  research 
on  rickettsiae  received  NIAID  support/^ 

In  addition  to  these  changes,  in  the  early  1970s  commercial  biologies 
houses  in  the  United  States  had  discontinued  production  of  specific 
rickettsial  antigens  for  diagnostic  tests.  Although  the  Centers  for  Dis- 
ease Control  continued  to  supply  these  antigens  to  state  health  lab- 
oratories and  to  other  designated  diagnostic  centers,  the  decline  in 
demand  for  such  services  v^as  reflected  in  the  relatively  few  institutions 
equipped  to  make  the  tests.  Reliance  on  the  broad-spectrum  antibiotics 
had  virtually  halted  efforts  to  improve  laboratory  tests.  Routine  lab- 
oratory diagnosis,  Richard  A.  Ormsbee  noted,  was  "no  better  in  1972 
than  it  was  at  the  close  of  World  War  II  in  1945."  He  warned  that 
"biomedical  competency  in  rickettsial  diseases"  in  the  United  States 
would  be  "largely  lost  within  the  next  10  years  if  these  trends  con- 
tinue." Ormsbee  also  described  a  parallel  situation  in  Western  Europe. 
"Laboratories  in  Brussels,  Paris,  Rome,  London,  and  Zurich,  which 
once  maintained  vigorous  programs  of  rickettsial  research  stimulated 
by  the  occurrence  during  World  War  II  of  Balkan  grippe  (Q  fever)  in 
Yugoslavia  and  Greece  and  by  epidemic  typhus  in  Egypt  and  Italy, 
now  are  mainly  devoted  to  other  subjects."  Conversely,  the  well-staffed 
laboratories  of  "Bratislava,  Bucharest,  and  Moscow"  continued  to 
support  research  on  rickettsial  diseases  vigorously.^^ 

Given  the  steady  erosion  in  the  numbers  of  young  investigators  and 
a  persistent  sense  that  rickettsial  diseases  posed  Httle  threat  to  the 
United  States,  it  is  doubtful  whether  any  individual  could  have  swayed 
institutional  priorities  on  behalf  of  rickettsiology  by  virtue  of  rhetoric 
alone.  What  did  help  to  reinvigorate  the  state  of  rickettsial  research 
in  the  United  States  was  an  unexplained  natural  phenomenon:  in  the 
1970s  the  incidence  of  Rocky  Mountain  spotted  fever  in  the  United 
States  began  to  rise  inexorably. 

In  1959,  Joseph  E.  Smadel  had  warned  that  changing  population 
patterns,  especially  the  creation  of  suburban  housing  developments 
near  large  east  coast  cities,  might  generate  a  rise  in  the  incidence  of 
spotted  fever.  Noting  that  this  region  was  an  endemic  area  of  the 
disease,  Smadel  cautioned  prospective  suburbanites  not  to  forget  the 
existence  of  "islands  of  infection"  of  Rickettsia  rickettsii,  which  or- 
dinarily were  maintained  in  "silence"  between  ticks  and  the  small 
animals  on  which  they  fed.  "Maryland  provides  an  example  in  point 
through  its  projected  urbanization  of  the  countryside  around  Baltimore 
and  Washington."  Even  before  the  upturn  in  cases  was  documented. 


spotted  Fever  after  Antibiotics 


2.35 


RATE 

e  oe- 

0  55- 


0  05- 

0  00—1 

1855  1000  \ OOB  <O-0  1875  ioe0  1O8S 

V  C  AP 

Reported  cases  of  Rocky  Mountain  spotted  fever  per  100,000  population, 
by  year,  in  the  United  States,  1955-83.  This  graph  reveals  the  surprising 
increase  in  Rocky  Mountain  spotted  fever  that  w^as  first  observed  in  1969. 
(Reproduced  from  D.  B.  Fishbein,  J.  E.  Kaplan,  K.  W.  Bernard,  and  W.  G. 
Winkler,  "Surveillance  of  Rocky  Mountain  Spotted  Fever,  United  States, 
1981-1983,"  Morbidity  and  Mortality  Weekly  Report,  CDC  Surveillance 
Summaries  33  [1984]:  15SS— 18SS.) 


Smadel's  prediction  appeared  prescient  to  many  who  monitored  the 
incidence  of  the  disease.  In  1965  a  group  of  researchers  concluded 
that  the  true  incidence  of  Rocky  Mountain  spotted  fever  was  actually 
"much  greater  than  the  number  of  reported  cases."  By  1970  the  num- 
bers were  clearer.  Michael  A.  W.  Hattwick  at  the  Centers  for  Disease 
Control  noted  that  reported  cases  in  the  United  States  had  increased 
from  200-300  per  year  during  the  1950s  to  498  in  1969.  The  case 
fatality  ratio  also  showed  "a  small  but  definite  rise"  since  i960.  Most 
of  these  cases  were  identified  in  the  southeast,  while  the  number  of 
cases  in  the  west  remained  low.  By  1977,  1,115  cases  were  reported 
in  the  United  States,  42  of  which  were  fatal.  Among  the  states  most 
afflicted,  North  Carolina,  Virginia,  Tennessee,  Maryland,  and  Okla- 
homa headed  the  list.^° 

In  1970  the  rise  in  spotted  fever  cases  stimulated  the  Centers  for 
Disease  Control  to  initiate  a  surveillance  program  that  reexamined  the 
epidemiology  and  clinical  features  of  spotted  fever.  The  first  five  years' 
data  gathered  from  this  study  confirmed  that,  although  a  problem 


Rocky  Mountain  Spotted  Fever 


existed,  it  had  not  yet  reached  the  proportions  of  the  pre-antibiotic 
era.  In  the  southeast  the  incidence  of  spotted  fever  reached  12  per 
miUion  in  1974,  one-sixth  of  the  76  per  miUion  recorded  in  the  Rocky 
Mountain  states  in  1935.  The  death-to-case  ratio,  moreover,  remained 
betvs^een  5  and  10  percent,  less  than  half  the  national  average  before 
antibiotics  were  introduced.  Epidemiologists  at  the  Centers  for  Disease 
Control  reported  that,  since  i960,  spotted  fever  cases  had  been  re- 
ported from  every  state  except  Alaska,  Hawaii,  Wisconsin,  Maine, 
and  Vermont.  Suggesting  that  a  change  in  population  patterns  might 
account  for  the  increase,  they  also  speculated  that  physicians  might 
be  recognizing  the  disease  more  frequently  than  in  the  past,  and  they 
postulated  that  a  cyclic  change  in  the  tick  vector  or  the  microorganism 
itself  could  be  involved. 

Coming  after  a  period  of  complacency  about  infectious  diseases,  the 
increasing  incidence  of  spotted  fever  seemed  unusual  to  many  epide- 
miologists. Some  attributed  it  to  a  gradual  invasion  of  the  eastern 
United  States  by  Rickettsia  rickettsii  from  the  Rocky  Mountain  regions. 
Others  postulated  that  the  western  R.  rickettsii  had  gradually,  and  for 
unknown  reasons,  become  avirulent  for  humans.  In  1977,  Willy  Burg- 
dorfer  at  the  Rocky  Mountain  Laboratory  dismissed  these  theories  as 
having  no  scientific  merit.  Historically,  he  pointed  out,  spotted  fever 
in  the  Rocky  Mountain  regions  was  "an  occupational  disease  among 
people  settling  in  enzootic  areas."  Once  the  land  was  cleared  and 
cultivated,  tick  infestation  decreased,  and  with  it,  the  incidence  of 
spotted  fever.  In  uncultivated  western  territories  that  remained  heavily 
populated  with  tick-infested  rodents,  Burgdorfer  observed,  people  con- 
tinued to  contract  the  disease  when,  during  a  short  pleasure  or  business 
outing,  they  became  "part  of  the  ecologic  cycle  of  R.  rickettsii.'"  In 
contrast,  spotted  fever  in  the  east  had  traditionally  been  "characterized 
by  high  incidence  among  children  and  women  — a  phenomenon  related 
to  infestations  of  household  pets,  particularly  dogs,  with  the  vector 
tick."  The  shift  of  eastern  populations  into  natural  foci  of  spotted  fever 
and  the  creation  of  wooded  recreational  areas  out  of  previously  cul- 
tivated land,  Burgdorfer  concluded,  adequately  explained  the  increas- 
ing incidence  of  the  disease  in  the  eastern  United  States. 

Ecological  factors  might  account  for  the  increase  in  incidence  of 
spotted  fever,  but  as  new  studies  charted  the  epidemiology  of  the 
disease,  a  few  surprises  emerged.  Overall  figures  were  consistent  with 
earlier  patterns.  Nearly  two-thirds  of  the  cases  occurred  in  children 
under  fifteen  years  old,  and  61  percent  of  the  patients  were  male.  Only 
52  percent  of  fatal  cases  were  in  young  people,  but  74  percent  were 
in  male  patients.  The  lower  death-to-case  ratio  in  female  patients, 


spotted  Fever  after  Antibiotics 


237 


especially  in  those  aged  fifteen  through  forty-four,  was  not  explained 
by  differing  rates  of  rash  or  tick  bite  — an  unexpected  finding.  It  sug- 
gested that  "a  degree  of  protection  against  fatal  Rocky  Mountain 
spotted  fever"  might  be  afforded  women  "during  their  reproductive 
years. "^^  Most  peculiar  was  the  relatively  high  13.9  percent  mortality 
among  black  male  victims.  It  was  more  than  double  the  5.8  percent 
recorded  for  white  males.  This  racial  difference,  CDC  epidemiologists 
found,  was  not  a  function  of  age.  They  believed  that  this  "very  high" 
death-to-case  ratio  in  black  males,  especially  in  those  younger  than 
ten,  could  be  explained  in  part  by  the  difficulty  of  observing  a  rash  in 
dark-skinned  patients.  Another  factor,  they  suggested,  might  be  the 
more  Hmited  access  to  medical  care  available  to  poorer  blacks  in  the 
United  States. This  analysis  was  consonant  with  the  social  concerns 
of  the  early  1970s,  but,  as  we  shall  see  in  chapter  12,  a  more  basic 
physiological  process  was  involved. 

In  198 1  the  number  of  cases  of  Rocky  Mountain  spotted  fever  in 
the  United  States  peaked  at  1,192,  a  national  incidence  of  51  cases 
per  million  people.  Beginning  in  that  year,  Oklahoma  became  the  state 
having  the  highest  incidence  of  cases  in  relation  to  its  population,  410 
per  million,  and  its  neighbors  Texas  and  Arkansas  also  reported  an 
increased  incidence  of  cases.  Despite  the  high  incidence,  Oklahoma 
recorded  only  397  cases  between  1981  and  1983,  while  heavily  pop- 
ulated North  Carolina,  the  state  with  the  greatest  number  of  cases, 
reported  736  during  this  period.  South  Carolina  with  288  cases  and 
Virginia  with  238  cases  were  the  third  and  fourth  most  infected  states 
in  the  early  1980s.  The  entire  "cycle"  of  increased  cases  appeared  to 
be  hmited  to  the  United  States,  for  no  reports  were  received  of  this 
phenomenon  in  other  western  hemisphere  countries. 

Across  the  Atlantic  Ocean,  however,  a  similar  increase  in  tick-borne 
rickettsioses  was  also  observed  and  first  reported  in  198 1  by  Vittorio 
Scaffidi,  an  Italian  rickettsial  researcher  located  in  Palermo,  Sicily. 
Between  World  War  II  and  the  mid  1970s,  he  noted,  cases  of  rickett- 
sioses of  all  kinds  had  been  reduced  to  "mere  sporadic  episodes."  Since 
1975,  however,  several  regions  of  Italy,  including  Lazio,  Liguria,  Sicily, 
and  Sardinia,  had  registered  "an  extraordinary  epidemiological  event." 
Boutonneuse  fever,  the  spotted  fever  group  disease  prevalent  through- 
out the  Mediterranean  basin,  had  increased  from  about  30  cases  per 
year  to  864  cases  in  1979.  Scaffidi  believed,  moreover,  that  the  actual 
number  of  cases  was  underreported  in  the  region.  He  speculated  that 
ecological  changes  involving  the  tick  vectors  of  boutonneuse  fever 
"must  be  presumed. "^^ 

Although  Scaffidi  noted  that  this  phenomenon  had  not  been  reported 


238 


Rocky  Mountain  Spotted  Fever 


elsewhere  in  the  Mediterranean  basin,  investigators  in  other  Mediter- 
ranean countries  soon  pubHshed  additional  accounts  of  the  unusual 
increase.  From  Israel  came  reports  that  from  six  cases  documented  in 
1973,  the  numbers  had  swelled  to  sixty-three  by  1978.^^  In  July  1982, 
Ferran  Segura  and  Bernat  Font  wrote  to  the  editor  of  Lancet  to  report 
an  increase  in  Spain  of  the  disease,  which  was  known  there  as  Med- 
iterranean spotted  fever.  A  total  of  seventeen  cases  had  met  their  clinical 
and  serological  criteria;  case  distribution  had  increased  from  two  in 
1978  to  six  in  198 1.  The  increase  had  been  confirmed  by  other  hospitals 
in  the  same  area,  and  most  cases  came  from  urban  areas.  Perhaps, 
they  speculated,  this  reflected  a  known  increase  in  the  number  of  pet 
animals  among  city  dwellers.  "Clearly  the  resurgence  in  Mediterranean 
Spotted  Fever  seen  in  Italy  is  also  happening  in  Spain,"  they  wrote, 
and  they  suggested  that  indeed  it  was  "a  pattern  common  to  the  whole 
geographical  area  in  which  this  disease  is  endemic."^^ 

This  unusual  increase  in  tick-borne  rickettsial  disease  stimulated 
renewed  research  in  the  Mediterranean  countries  and  led  as  well  to 
fruitful  international  collaborations.^^  The  Sicilian  group,  for  example, 
led  by  Scaffidi's  colleagues  Serafino  Mansueto  and  Giuseppe  TringaH, 
began  studying  boutonneuse  fever's  epidemiology  in  western  Sicily  and 
the  persistence  of  antibodies  to  R.  conorii  in  humans  and  in  dogs.  In 
the  1930s  dogs  had  been  shown  susceptible  to  infection  with  tick- 
borne  rickettsial  diseases.  They  also,  of  course,  could  bring  infected 
ticks  into  the  homes  of  their  human  owners. All  of  this  research 
revealed  that  although  the  basic  pathological  physiology  of  the  tick- 
borne  rickettsial  diseases  had  been  described,  much  remained  unknown 
in  the  last  decades  of  the  twentieth  century  about  their  natural  histories. 

Diagnosis  of  Rocky  Mountain  spotted  fever  also  continued  to  be 
difficult  in  atypical  cases,  a  situation  underscored  in  a  1977  tragedy 
at  the  Centers  for  Disease  Control  in  Atlanta,  Georgia.  In  mid  February 
Robert  Dubington,  a  building  custodian,  and  George  Flowers,  a  ware- 
houseman, both  of  whom  worked  in  the  same  building  at  the  CDC, 
were  hospitalized  with  symptoms  of  high  fever,  nausea,  diarrhea,  and 
vomiting.  Mental  confusion  and  convulsions  followed,  but  no  rash 
was  observed.  Flowers  died  on  27  February,  and  Dubington  died  two 
days  later,  on  i  March.  Initially,  Legionnaires'  disease,  the  mysterious 
bacterial  malady  that  had  struck  unexpectedly  in  1976  and  was  under 
investigation  at  the  CDC,  was  suspected  in  these  deaths.  Post-mortem 
studies,  however,  revealed  that  both  men  had  died  from  Rocky  Moun- 
tain spotted  fever.  It  remained  unclear  how  they  contracted  the  disease, 
for  neither  had  routine  access  to  laboratory  areas. 

Plainly  this  disease,  thought  "conquered"  in  1948,  retained  the  abil- 


spotted  Fever  after  Antibiotics 


239 


ity  to  wreak  misery  and  death.  The  resurgence  of  Rocky  Mountain 
spotted  fever  in  the  United  States  thus  accompHshed  what  rickettsial 
investigators  had  been  unable  to  achieve  by  exhorting  their  colleagues. 
A  new  generation  of  investigators,  many  of  whom  were  too  young  to 
recall  the  pre-antibiotic  era,  were  challenged  to  apply  their  training  in 
immunology,  in  molecular  biology,  and  in  other  new  fields  to  the 
problem  of  Rocky  Mountain  spotted  fever.  By  1980  a  new  professional 
organization,  the  American  Society  of  Rickettsiology  and  Rickettsial 
Diseases,  had  been  formed. Junior  and  senior  rickettsiologists  col- 
laborated in  reexamining  diagnostic  tests,  vaccines,  chnical  knowledge, 
and  therapy.  In  this  task,  they  could  draw  on  the  body  of  basic  research 
accumulated  since  World  War  II  that  provided  information  about  rick- 
ettsial organisms  essential  to  formulating  new  strategies  against  the 
disease. 


Chapter  Twelve 


Mysteries  Explained, 
Mysteries  Remaining 


All  interest  in  disease  and  death  is  only  another  expression  of 
interest  in  life. 

Thomas  Mann,  The  Magic  Mountain 


"The  easiest  way  to  lose  ground  in  the  fight  against  infectious  dis- 
eases," wrote  Harry  DowHng  in  1977,  "is  to  assume  that  they  have 
been  conquered  and  nothing  more  needs  to  be  done."^  The  dangers 
of  such  neglect  became  obvious  in  relation  to  Rocky  Mountain  spotted 
fever  during  its  surprising  upsurge  in  the  1970s.  Although  a  number 
of  advances  in  understanding  the  basic  biology  of  rickettsiae  had  been 
made  since  World  War  II,  virtually  no  new  methods  of  diagnosis, 
prevention,  or  therapy  had  been  developed.  This  situation  suggests 
that,  in  the  United  States,  active  programs  of  research  on  any  disease 
are  difficult  to  sustain  without  the  stimulus  of  an  imminent  disease 
threat.  In  examining  the  recent  history  of  spotted  fever,  however,  it  is 
also  clear  that  rapid  advancement  in  applied  fields  since  1970  largely 
depended  upon  the  advances  in  basic  research  fields  made  during 
spotted  fever's  quiescent  decades  between  1950  and  1970.  Efforts  to 
control  and  combat  this  disease  of  nature  are  still  under  way,  and  any 
definitive  evaluation  of  these  endeavors  will  require  a  longer  historical 
perspective.  Several  long  standing  mysteries  raised  by  spotted  fever 
have  been  solved,  however,  and  those  that  remain  suggest  directions 
for  future  inquiry. 

When  spotted  fever  began  to  increase  during  the  1970s,  renewed 
chnical  studies  of  the  disease  confirmed  older  assessments  of  the  grave 
danger  posed  by  infections  with  Rickettsia  rickettsii.  Circulatory  col- 
lapse, kidney  failure,  and  neurological  damage  were  all  potential 
threats.  Since  19 19,  when  S.  Burt  Wolbach  published  his  major  review 
of  the  disease,  spotted  fever  had  been  understood  as  an  affliction  of 
the  circulatory  system.  From  the  1940s  through  the  1960s,  occasional 


240 


Mysteries  Explained,  Mysteries  Remaining 


241 


papers  had  discussed  specific  cardiac  complications  of  spotted  fever 
and  their  treatment.  At  the  end  of  the  1970s,  however,  new  research 
indicated  that  the  disease  did  not  cause  significant  loss  of  heart  function. 
The  greater  danger  appeared  to  be  the  threat  to  the  circulatory  tree, 
as  had  been  suggested  in  World  War  11.^ 

In  contrast  to  an  early  appreciation  of  spotted  fever's  effect  on  the 
circulatory  system,  it  was  not  until  the  1950s  that  its  full  potential 
impact  on  the  brain  was  appreciated.  In  1947  a  physician  in  Ann 
Arbor,  Michigan,  had  queried  the  editor  of  the  journal  of  the  American 
Medical  Association  about  long-term  neurological  effects  from  spotted 
fever.  The  Journal's  editor  had  restated  the  position  taken  at  that  time 
by  most  textbook  authors.  Headache,  hearing  loss,  lethargy  or  rest- 
lessness, mental  confusion,  and  sometimes  delirium  characterized  the 
disease  during  the  acute  course,  but  these  afflictions  were  expected  to 
last  only  a  few  weeks. ^  Later  studies  disputed  this  conclusion,  noting 
that  infection  with  Rickettsia  rickettsii  could  destroy  the  myelin  sheath 
around  nerves  and  cause  the  formation  of  granulomatous  tissue  in  the 
brain."^  "Pathologic  examination  reveals  greater  damage  to  the  brain 
in  spotted  fever  than  in  any  other  rickettsial  disease,"  concluded  one 
group  of  investigators  in  1952.^ 

In  its  most  severe  form,  spotted  fever  may  mimic  other  diseases, 
especially  acute  appendicitis.  The  pathological  physiology  of  these 
abdominal  symptoms  is  not  yet  understood,  but,  as  the  authors  of 
another  recent  paper  noted,  they  "underscore  the  protean  manifes- 
tations" of  spotted  fever.^  The  mechanism  by  which  the  organism 
damages  human  cells  is  also  just  beginning  to  be  understood.  "Evidence 
is  accumulating,"  wrote  David  H.  Walker  of  the  University  of  North 
Carolina  School  of  Medicine  at  Chapel  Hill  in  1982,  "that  injury  occurs 
to  the  cell  membrane  on  penetration  into  and  release  from  the  host 
cell  by  rickettsiae."^ 

During  the  1970s,  Walker  and  his  colleagues  initiated  a  variety  of 
studies  on  Rocky  Mountain  spotted  fever  because  of  their  location  in 
North  Carolina,  an  endemic  spotted  fever  area  reporting  a  large  num- 
ber of  cases  each  year.  During  and  after  World  War  II,  the  state's  high 
incidence  had  spurred  George  T.  Harrell,  Jerry  K.  Aikawa,  and  their 
colleagues  at  the  Bowman  Gray  School  of  Medicine  of  Wake  Forest 
University  in  Winston-Salem  to  conduct  studies  on  clinical  problems 
associated  with  the  disease,  especially  capillary  permeability  and  fluid 
loss.  A  clinical  review  paper  written  by  Harrell  in  1949  stood  for 
decades  as  definitive  in  clinical  practice,  and  in  1966,  Aikawa  published 
a  monograph  on  spotted  fever  that  summarized  much  of  this  work.^ 


242 


Rocky  Mountain  Spotted  Fever 


Walker's  group  continued  this  North  Carohna  tradition,  focusing  es- 
pecially on  clinical  and  epidemiological  studies. 

One  problem  they  solved,  for  example,  was  the  mystery  of  high 
spotted  fever  mortality  in  black  males,  a  phenomenon  noted  in  1976 
by  epidemiologists  at  the  Centers  for  Disease  Control.  Two  tentative 
explanations  had  been  offered  at  that  time:  the  difficulty  of  identifying 
a  typical  spotted  fever  rash  on  dark  skin  and  diminished  access  to 
medical  care,  a  problem  common  to  lower  socioeconomic  groups. 
Neither  rationale  proved  satisfactory,  because  black  females,  who 
shared  both  criteria,  exhibited  a  mortality  rate  no  higher  than  did 
white  females.  The  figures  instead  suggested.  Walker  and  his  colleagues 
believed,  the  existence  of  some  sex-linked  genetic  condition  that  oc- 
curred primarily  among  blacks  and  rendered  males  more  vulnerable. 
It  was  known  that  about  12  percent  of  American  black  males  suffered 
from  a  glucose-6-phosphate  dehydrogenase  (G6PD)  deficiency,  a  ge- 
netic-linked metabolic  disorder  much  less  common  in  whites  and  in 
black  females.  The  North  Carolina  group  therefore  studied  the  fre- 
quency of  G6PD  deficiency  among  black  males  who  died  from  spotted 
fever  and,  indeed,  found  that  the  incidence  was  much  higher  than 
expected.  "Ultimately,"  they  concluded,  "G6PD-deficient  persons  may 
represent  a  target  population  for  an  effective  vaccine  against  Rocky 
Mountain  spotted  fever."^ 

In  addition  to  black  males  with  a  G6PD  deficiency,  several  other 
groups  of  people  at  high  risk  were  identified  as  potential  candidates 
for  vaccination  against  spotted  fever.  One  large  cluster  was  comprised 
of  children  and  adults  living  in  highly  infected  districts,  especially  those 
with  existing  medical  problems  that  might  become  hfe-threatening 
under  the  strain  of  a  severe  infection.  Army  recruits  training  in  "tick 
belt"  states  made  up  another  population  at  risk.^°  Laboratory  per- 
sonnel, although  a  relatively  small  group,  were  often  exposed  to  highly 
virulent  strains  of  spotted  fever,  as  the  fatal  cases  sustained  by  many 
early  laboratory  martyrs  attested  (see  Table  4).  The  two  1977  deaths 
at  the  Centers  for  Disease  Control,  moreover,  prompted  a  letter  to  the 
editor  of  the  New  England  Journal  of  Medicine  in  support  of  vaccine 
development  for  the  protection  of  laboratory  workers.  Even  before 
this  tragedy,  other  concerned  scientists  had  published  a  number  of 
studies  on  the  risks  of  laboratory  infection. 

When  the  1970s  increase  in  spotted  fever  cases  renewed  interest  in 
protective  vaccination,  however,  the  only  vaccine  available  was  the 
Cox  yolk  sac  product,  which  had  been  produced  virtually  unchanged 
by  Lederle  Laboratories  since  the  1940s.  The  first  clear  indication  that 
the  state  of  spotted  fever  prophylaxis  was  unacceptable  came  in  1973, 


Mysteries  Explained,  Mysteries  Remaining 


2.43 


TABLE  4.  Deaths  from  Laboratory- Acquired  Spotted  Fever 
Infections 


Year 


Name 


Position 


1912  Thomas  B.  McClintic 

1918  Stephen  MoHnscek 

1919  Arthur  H.  McCray 
1922  WilHam  E.  Gettinger 
1924  George  Henry  Cowan 

1928  Albert  LeRoy  Kerlee 

1927  Elisabeth  Brandt 

1931  Kokyo  Sugata 

1932  Masajiro  Nishibe 

1935  Jose  Lemos  Monteiro 

1935  Edison  de  Andrade  Dias 

1942  Hector  Calderon  Cuervo 

1977  Robert  Dubington 

1977  George  Flowers 


Passed  Assistant  Surgeon,  U.S.  Public 
Health  Service 

Laboratory  assistant  to  Hideyo  Noguchi, 
Rockefeller  Institute  for  Medical 
Research 

Bacteriologist,  Montana  State  Board 
of  Health 

Student  assistant,  U.S.  Public  Health 
Service 

Field  assistant,  Montana  State  Board  of 
Entomology  and  U.S.  Public  Health 
Service 

Student  assistant,  U.S.  PubHc  Health 
Service 

Laboratory  technician  for  Max 
Kuczynski,  Berlin 

Assistant  to  Norio  Ogata,  Chiba  Medical 
College,  Japan 

Professor,  Niigata  Medical  College, 
Japan 

Brazilian  investigator,  Butantan  Institute, 
Sao  Paulo,  Brazil 
Monteiro's  assistant 
Investigator  in  Bogota,  Colombia 
Building  custodian,  U.S.  Centers  for 
Disease  Control 

Warehouseman,  U.S.  Centers  for  Disease 
Control 


when  a  seven-member  team  of  researchers  led  by  Herbert  L.  DuPont 
at  the  University  of  Maryland  School  of  Medicine  in  Baltimore  tested 
stored  samples  of  the  Spencer-Parker  tick  tissue  vaccine  and  com- 
mercially produced  Cox  yolk  sac  vaccine.  Groups  of  volunteers  from 
the  Maryland  House  of  Correction  in  Jessup,  Maryland,  w^ho  had  been 
informed  of  the  risks  involved  and  advised  that  they  could  w^ithdraw 
from  the  study  at  any  time,  w^ere  inoculated  with  one  of  the  vaccines 
or  left  unvaccinated  as  controls.  Subsequently  each  was  injected  with 
a  large  dose  of  virulent  R.  rickettsii.  All  developed  cases  of  Rocky 


244 


Rocky  Mountain  Spotted  Fever 


Mountain  spotted  fever  and  were  treated.  The  results  of  this  test  were 
unequivocal:  neither  type  of  spotted  fever  vaccine  prevented  the  dis- 
ease. 

This  finding  would  not  have  been  surprising  to  the  original  producers 
of  those  vaccines,  whose  own  studies  revealed  that  they  lessened  the 
severity  of  infection  rather  than  preventing  it.  In  the  1920s  and  1930s 
when  the  Spencer-Parker  and  Cox  vaccines  were  developed,  human 
trials  with  virulent  organisms  were  unthinkable,  because  no  therapy 
existed  that  could  cure  a  severe  case  of  the  disease.  Instead,  the  vaccines 
had  been  tested  in  experimental  animals  for  efficacy,  purity,  and  po- 
tency. After  the  development  of  broad-spectrum  antibiotics,  the  need 
for  any  vaccine  seemed  minimal,  and  no  work  had  been  done  to 
improve  the  existing  product. 

About  the  time  the  DuPont  study  was  published,  Richard  H.  Kenyon, 
WiUiam  M.  Acree,  George  G.  Wright,  and  Fred  W.  Melchoir,  Jr., 
members  of  the  U.S.  Army  Medical  Research  Institute  of  Infectious 
Diseases  at  Fort  Detrick  in  Frederick,  Maryland,  reported  that  they 
had  prepared  a  new  candidate  vaccine  against  Rocky  Mountain  spotted 
fever.  Using  R.  rickettsii  propagated  in  tissue  cultures  of  chick  embryo 
cells  rather  than  in  the  chick  embryos  themselves,  the  group  prepared 
two  vaccines  for  testing  in  guinea  pigs.  The  first  was  irradiated  to  kill 
the  rickettsiae,  a  procedure  based  on  recent  studies  with  tularemia  and 
psittacosis  organisms  indicating  that  vaccines  killed  by  ionizing  ra- 
diation retained  greater  antigenicity  than  those  killed  by  heat  or  chem- 
icals. The  second  vaccine  was  treated  with  formaldehyde  to  kill  rick- 
ettsiae. Initial  tests  on  guinea  pigs  demonstrated  that  both  cell  culture 
vaccines  were  more  than  nine  hundred  times  as  active  as  the  old  yolk 
sac  vaccine.  Surprisingly,  the  vaccine  prepared  with  formaldehyde 
proved  superior  to  the  irradiated  vaccine  in  protecting  guinea  pigs 
from  direct  challenge  with  R.  rickettsii.  Over  the  next  few  years,  the 
army  group  worked  to  improve  the  formaldehyde  cell  culture  vaccine 
by  various  techniques  and  to  conduct  initial  tests  of  its  efficacy  in 
animals  and  safety  for  humans. 

In  October  1976,  however.  Congress  withdrew  all  funds  for  the 
army's  spotted  fever  vaccine  program,  arguing  that  it  duplicated  re- 
search efforts  at  the  National  Institute  of  Allergy  and  Infectious  Dis- 
eases. Shortly  thereafter,  WiUiam  S.  Augerson,  commanding  general 
of  the  U.S.  Army  Medical  Research  and  Development  Command,  wrote 
to  the  NIAID  director,  Richard  Krause,  requesting  that  "NIAID  assume 
responsibility  for  completion  of  qualifications  necessary  to  license  this 
RMSF  vaccine  for  human  use."  After  reviewing  the  proposed  vaccine's 
promise,  the  potential  population  that  would  benefit  from  vaccine 


Mysteries  Explained,  Mysteries  Remaining 


2-45 


development,  and  the  program's  cost,  Robert  Edelman,  chief  of  the 
Chnical  Studies  Branch  in  NIAID's  Microbiology  and  Infectious  Dis- 
eases Program,  won  concurrence  from  the  director  of  the  program, 
WiUiam  Jordan,  to  recommend  that  the  institute  sponsor  the  work.^^ 

On  30  October  1978  the  NIAID  Microbiology  and  Infectious  Dis- 
eases Advisory  Committee  considered  plans  for  testing  the  candidate 
vaccine.  Samuel  L.  Katz,  chairman  of  the  Department  of  Pediatrics  at 
Duke  University  Medical  Center,  urged  the  committee  to  go  forward 
with  clinical  trials  of  the  candidate  army  vaccine.  "Because  our  state 
reports  the  largest  number  of  cases  each  year  of  any  throughout  the 
nation,"  Katz  stated,  "we  have  come  to  speak  of  the  disease  as  North 
Carolina  Tick  Typhus."  Buttressing  the  case  that  a  large  potential 
population  for  the  vaccine  existed,  Katz  noted  that  North  Carolina 
physicians  actually  treated  1,524  cases  of  suspected  spotted  fever  each 
year,  in  contrast  to  the  200  cases  they  reported  to  the  CDC.^^ 

The  advisory  committee  agreed  that  the  program  should  continue, 
but  it  recommended  that  before  any  direct  human  trials  were  con- 
ducted, two  other  studies  should  be  done.  "A  careful  and  intense 
epidemiologic  study  was  needed  to  clearly  determine  the  incidence  and 
importance  of  the  disease  and  to  define  populations  in  which  the 
usefulness  of  the  vaccine  in  preventing  disease  in  humans  might  later 
be  determined."  In  addition,  the  committee  recommended  that  a  pri- 
mate model  be  developed  in  order  to  study  "the  nature  of  the  disease, 
the  immune  response  to  infection  and  the  safety,  immunogenicity  and 
efficacy  of  candidate  vaccines."^" 

Reasons  for  such  a  cautious  approach  were  articulated  by  John  R. 
Seal,  NIAID  deputy  director.  Noting  the  relatively  small  size  of  the 
population  that  would  seek  protection  from  a  new  spotted  fever  vac- 
cine. Seal  noted  that  few  commercial  laboratories  were  likely  to  be 
interested  in  producing  it.  "Here  we  seem  to  be  on  a  track  of  a  limited 
use  vaccine  which,  under  present  law,  would  have  to  be  dispensed  by 
the  CDC  under  IND  [investigational  new  drug]  regulations."  More 
importantly.  Seal  was  concerned  about  whether  the  new  vaccine  would 
be  any  more  effective  than  the  old  Cox  vaccine,  which  lessened  the 
severity  of  the  disease  but  did  not  prevent  it.^^ 

The  recommended  preliminary  studies  were  implemented,  and  the 
epidemiologic  data  provided  somewhat  surprising  results.  Catherine 
M.  Wilfert  at  Duke  University  Medical  Center  led  a  team  of  researchers 
in  identifying  cases  of  spotted  fever  that  could  be  serologically  con- 
firmed in  two  North  CaroHna  counties.  In  contrast  to  the  estimates 
by  physicians  that  many  more  cases  occurred  than  were  reported, 
Wilfert  and  colleagues  found  that  only  one  of  three  reported  cases 


Rocky  Mountain  Spotted  Fever 


exhibited  antibodies  in  the  blood.  Although  no  primate  model  was 
developed  for  broad  studies  on  the  nature  of  spotted  fever  infection, 
the  candidate  vaccine  w^as  tested  in  guinea  pigs.  Results  indicated  that 
it  protected  them  only  partially  from  infection  w^ith  virulent  R.  rick- 
ettsii.  As  with  the  older  vaccines,  higher  doses  and  frequent  booster 
injections  increased  protection. 

The  ambiguities  in  these  findings  raised  questions  about  the  vaccine's 
probable  efficacy  as  well  as  the  number  of  people  who  might  benefit 
from  it.  Ten  years  of  research  had  been  invested  in  the  product,  how- 
ever, and  in  1983  a  placebo-controlled  double-blind  study  in  humans 
was  conducted  by  a  group  led  by  Mary  L.  Clements  at  the  Center  for 
Vaccine  Development  of  the  University  of  Maryland  School  of  Med- 
icine in  Baltimore.  Of  the  fifty-two  volunteers  vaccinated,  sixteen  were 
challenged  with  virulent  R.  rickettsii  one  month  after  vaccination.  Six 
unvaccinated  volunteers  also  received  the  challenge  dose  as  controls. 
The  results  of  this  test  were  only  marginally  better  than  in  the  DuPont 
study.  Twelve  of  the  sixteen  vaccinated  volunteers  developed  typical 
Rocky  Mountain  spotted  fever,  as  did  all  the  controls.  As  with  the 
earlier  vaccines,  the  incubation  period  was  longer,  the  duration  of 
constitutional  symptoms  shorter,  and  the  height  of  fever  lower  in  the 
vaccinated  volunteers.  "The  vaccine  provided  only  partial  protection 
against  Rocky  Mountain  spotted  fever,"  concluded  the  investigators. 

The  failure  of  this  new  vaccine  to  provide  complete  protection 
against  spotted  fever  dashed  the  hopes  of  anyone  seeking  vaccination 
against  the  disease.  In  1980,  while  the  army  vaccine  was  still  being 
developed,  a  U.S.  Food  and  Drug  Administration  panel  comprised  of 
leading  rickettsiologists,  pediatricians,  and  virologists  had  evaluated 
the  efficacy  and  safety  of  Lederle  Laboratories's  yolk  sac  vaccine.  Citing 
the  1973  DuPont  study,  the  members  of  the  Food  and  Drug  Admin- 
istration panel  expressed  little  confidence  in  the  product's  efficacy. 
They  noted  that  between  1969  and  1972  there  had  been  no  complaints 
about  its  safety;  however,  they  observed,  this  "probably  indicated  more 
the  failure  to  report  complaints  than  inherent  safety."  The  panel 
awarded  the  vaccine  "an  unfavorable  benefit/risk  ratio,"  and  assigned 
it  category  III-A  status,  which  meant  that  it  could  remain  commercially 
available  pending  completion  of  additional  tests.  The  decision,  how- 
ever, was  moot.  On  11  June  1979,  even  before  the  panel  met,  Lederle 
Laboratories  had  requested  that  its  license  to  produce  spotted  fever 
vaccine  by  the  yolk  sac  method  be  revoked  and  had  withdrawn  the 
product  from  the  market.^^ 

It  is  likely  that  both  the  caution  of  the  Food  and  Drug  Administration 
panel  and  the  decision  of  Lederle  Laboratories  were  influenced  by 


Mysteries  Explained,  Mysteries  Remaining 


^47 


more  than  dispassionate  scientific  inquiry.  By  the  1970s  the  pubhc  had 
become  more  wiUing  to  sue  commercial  producers  of  vaccines  when 
products  failed  or  caused  toxic  side  effects.  Because  U.S.  law  placed 
financial  responsibility  on  vaccine  producers  for  the  statistically  pre- 
dictable number  of  injuries  and  deaths  that  occur  from  widespread 
vaccination  programs,  firms  such  as  Lederle  often  reduced  their  liability 
by  halting  production  of  products  considered  risky.  When  the  number 
of  potential  vaccine  recipients  was  small,  as  in  the  case  of  Rocky 
Mountain  spotted  fever,  commercial  advantage  was  completely  over- 
shadowed by  considerations  of  liability.  Even  though  no  suit  had  been 
brought  over  Lederle's  spotted  fever  vaccine,  the  company's  swift  ac- 
tion reflected  a  larger  problem  that  has  yet  to  be  resolved. 

The  groups  involved  in  assessing  the  failure  of  the  old  yolk  sac  and 
new  tissue  culture  vaccines  arrived  at  the  same  conclusion  about  why 
neither  provided  full  protection.  Basing  their  evaluations  on  new  dis- 
coveries in  immunology  made  during  the  preceding  decades,  the  FDA 
panel,  the  DuPont  group,  and  the  Clements  group  speculated  that  the 
humoral  immunity  stimulated  by  the  vaccines  was  insufficient  to  pro- 
vide full  protection  against  the  disease.  Although  additional  research 
on  the  immune  response  in  spotted  fever  infections  must  be  done  before 
conclusive  proof  can  be  presented,  they  suggested  that  recovery  from 
a  frank  spotted  fever  infection  probably  produced  immunity  mediated 
by  cellular  rather  than  by  humoral  mechanisms,  because  there  was  no 
correlation  between  the  presence  of  antibodies  in  serum  and  protection 
from  the  disease. 

Although  these  two  types  of  immunity  had  been  known  since  the 
late  nineteenth  century,  detailed  knowledge  about  their  components, 
mechanisms,  and  interactions  had  only  begun  to  be  elucidated  in  the 
1960s.  The  humoral  immune  system,  named  from  the  historic  usage 
of  the  word  humors  for  body  fluids,  was  shown  to  function  through 
the  actions  of  specialized  white  blood  cells,  called  B  cells,  which  pro- 
duce antibodies  against  foreign  antigens  on  the  surface  of  invading 
organisms.  Circulated  throughout  the  blood  and  other  body  fluids, 
these  antibodies  are  most  effective  against  bacteria,  their  toxins,  and 
viruses  present  in  body  fluids.  The  cell-mediated  immune  system,  com- 
prised of  other  white  blood  cells,  especially  those  known  as  T  cells, 
works  in  addition  to  the  humoral  system.  The  T  ceUs  do  not  produce 
antibodies,  but  they  coordinate  attacks  by  several  other  types  of  white 
cells  against  cancer  cells,  transplanted  tissue,  and  intracellular  bacteria 
and  viruses.  Rickettsia  rickettsii,  of  course,  falls  into  the  last  category. 

These  concepts  helped  to  explain  another  longstanding  mystery  of 
spotted  fever  and  possibly  pointed  the  way  toward  a  more  successful 


Rocky  Mountain  Spotted  Fever 


vaccine.  Howard  Taylor  Ricketts  had  first  attempted  to  treat  spotted 
fever  victims  with  immune  serum  taken  from  people  or  animals  that 
had  recovered  from  a  spotted  fever  infection.  All  such  immune  sera 
failed  to  effect  the  dramatic  cures  possible  when  diphtheria  patients 
were  treated  similarly.  Diphtheria,  of  course,  is  caused  by  the  action 
of  a  toxin,  which  is  rapidly  rendered  harmless  by  the  antibodies  present 
in  immune  sera.  Spotted  fever  rickettsiae,  in  contrast,  inhabit  the  cells 
of  the  host,  where  they  are  protected  from  antibody  attack. 

Because  both  the  Spencer-Parker  and  the  Cox  spotted  fever  vaccines 
had  utilized  killed  rickettsiae,  furthermore,  they  may  not  have  stim- 
ulated cell-mediated  immunity  as  did  recovery  from  an  active  case  of 
the  disease.  In  contrast,  a  number  of  vaccines  against  viral  diseases 
such  as  rabies,  yellow  fever,  and  poHo  were  prepared  from  attenuated  — 
that  is,  weakened  but  not  killed— strains  of  virus.  Such  products  mim- 
icked active  infection  and  produced  cell-mediated  immunity  without 
the  risk  of  severe  disease.  Howard  Taylor  Ricketts  had  attempted 
without  luck  to  attenuate  the  spotted  fever  organism  early  in  the 
century,  and  after  the  development  of  the  Spencer-Parker  vaccine, 
further  efforts  to  attenuate  the  organism  had  been  abandoned. 

Between  1974  and  the  mid  1980s,  several  groups  of  investigators 
launched  projects  aimed  at  designing  a  vaccine  to  produce  the  complete 
protection  stimulated  only  by  frank  infection  with  the  disease  or  by 
a  successful  attenuated  vaccine. Using  a  variety  of  techniques  de- 
veloped by  molecular  biologists,  they  first  focused  .on  identifying  in- 
dividual surface  proteins  of  Rickettsia  rickettsii  that  might  serve  as 
antigens  in  an  improved  vaccine.  In  reviewing  this  work,  Hui  Min 
Feng,  Celia  Kirkman,  and  David  H.  Walker  at  the  University  of  North 
Carolina  School  of  Medicine  observed  that  one  series  of  these  studies 
produced  a  "reasonable  catalogue"  of  approximately  thirty-five  rick- 
ettsial proteins.  Another  group  of  studies  utilized  monoclonal  anti- 
bodies and  the  methods  of  immunoblotting  and  radioimmunoprecip- 
itation  to  analyze  these  proteins  as  antigens. 

Gregory  A.  McDonald,  Robert  L.  Anacker,  and  Kareen  Garjian  at 
the  Rocky  Mountain  Laboratories  cloned  the  gene  for  one  of  these 
antigens  in  Escherichia  coli  bacteria  and  tested  the  effectiveness  of  the 
recombinant-DNA  product  as  a  vaccine  against  Rocky  Mountain  spot- 
ted fever.  They  reported  that  the  material  protected  mice  from  a  lethal 
dose  of  virulent  R.  rickettsii.  Although  this  candidate  vaccine  faces 
years  of  refinement  and  testing,  it  may  prove  to  be  the  hoped-for 
effective  and  safe  preventative  against  spotted  fever.^^ 

Since  no  vaccine  is  available  at  present,  and  since  relatively  few 
people  at  occasional  risk  of  contracting  spotted  fever  would  be  vac- 


Mysteries  Explained,  Mysteries  Remaining 


249 


cinated  in  any  case,  the  key  to  effective  therapy  is  rapid  diagnosis.  The 
increase  in  spotted  fever  incidence  during  the  1970s  also  stimulated  a 
renewed  interest  in  diagnostic  tests,  which,  like  the  vaccine,  had  not 
been  significantly  improved  since  World  War  11.  As  late  as  1976,  for 
example,  Charles  C.  Shepard  and  his  associates  at  the  Centers  for 
Disease  Control  stated  flatly,  "No  laboratory  diagnostic  procedure  is 
now  available  that  will  provide  a  specific  laboratory  diagnosis  in  time 
to  help  the  physician  in  his  decision  about  therapy"  in  suspected  spotted 
fever  cases. ^" 

In  1978  another  CDC  study— this  one  on  the  characteristics  most 
frequently  associated  with  fatal  Rocky  Mountain  spotted  fever— re- 
iterated the  need  for  more  accurate  diagnostic  tests.  Delay  in  seeking 
treatment  proved  not  to  be  an  important  factor  associated  with  dying 
from  spotted  fever.  The  high  fever  and  debility  accompanying  the 
disease  sent  most  patients  to  a  physician  at  about  the  same  time.  The 
average  amount  of  time  that  elapsed  between  the  onset  of  illness  and 
the  initiation  of  appropriate  therapy,  however,  was  more  than  two 
days  longer  for  fatal  than  for  nonfatal  cases.  When  patients  who  later 
died  first  visited  a  physician,  the  study  noted,  they  rarely  displayed  the 
classic  diagnostic  triad  of  fever,  rash,  and  history  of  tick  bite.  Instead, 
they  presented  nonspecific  symptoms,  such  as  fever,  headache,  and 
malaise,  which  were  characteristic  of  several  diseases.  Gastrointestinal 
complaints,  including  nausea,  vomiting,  abdominal  pain,  and  diarrhea, 
were  also  prominent  symptoms  in  approximately  one-third  of  the  fatal 
cases  and  were  present  in  only  4  percent  of  those  who  recovered. 
Because  of  these  puzzling  initial  symptoms,  the  critical  history  of 
whether  the  patient  had  been  bitten  by  a  tick  was  obtained  three  days 
later  among  fatal  cases  than  it  was  from  those  who  recovered.  In  short, 
those  patients  who  were  treated  with  an  antirickettsial  broad-spectrum 
antibiotic  within  the  first  five  days  of  illness  usually  recovered,  while 
all  but  two  of  the  fatal  cases  studied  were  not  treated  before  the  sixth 
day  of  illness.  "The  major  problem  in  diagnosis  appears  to  be  the 
presence  of  nonspecific  or  misleading  symptoms  occurring  before  onset 
of  rash,"  the  authors  concluded. 

What  was  clearly  needed  was  a  laboratory  test  that,  no  matter  what 
symptoms  were  present,  could  rapidly  demonstrate  whether  the  patient 
was  infected  with  R.  rickettsii}^  In  their  search  for  such  a  test,  inves- 
tigators in  the  1970s  first  reviewed  the  research  of  previous  decades, 
hoping  to  find  leads  to  exploit.  In  the  early  1950s,  R.  Shin-man  Chang, 
Edward  S.  Murray,  and  John  C.  Snyder  at  the  Harvard  University 
School  of  Public  Health  had  discovered  that  sera  from  spotted  fever 
patients  as  early  as  six  days  after  the  onset  of  illness  agglutinated 


250 


Rocky  Mountain  Spotted  Fever 


human  group  O  erythrocytes,  or  red  blood  cells,  after  the  erythrocytes 
were  sensitized  with  substances  extracted  by  ether  from  suspensions 
of  infected  yolk  sac  membranes.  This  diagnostic  test,  called  the  indirect 
hemagglutination  (IHA)  test,  proved  more  sensitive  and  technically 
simpler  than  the  complement  fixation  test.  Very  little  active  material 
was  required— enough  could  be  prepared  from  one  infected  yolk  sac 
to  test  at  least  five  hundred  sera.  This  procedure,  however,  had  never 
been  developed  commercially.  It  had  not  been  found  superior  to  the 
complement  fixation  test,  and  because  of  the  generally  low  level  of 
interest  in  spotted  fever  during  the  1950s,  the  older  technique  had 
remained  the  standard  laboratory  procedure. ^° 

Nearly  two  decades  later,  with  spotted  fever  on  the  rise,  several 
investigators  sought  to  improve  the  IHA  test.  One  group  introduced 
the  use  of  stabilized  sheep  erythrocytes  so  that  the  test  could  be  per- 
formed under  field  conditions.  Another  team  adapted  the  test  to  mi- 
crotiter  plates  and  employed  the  technique  known  as  sucrose  density 
gradient  centrifugation  to  purify  antigen  from  R.  rickettsii.  With  these 
changes,  the  IHA  test  provided  positive  results  in  a  greater  percentage 
of  cases  than  did  the  complement  fixation  test.^^  The  microagglutina- 
tion  test,  developed  in  1969,  and  the  latex  agglutination  test,  developed 
in  1980,  provided  two  additional  variations  on  this  technique.  The 
microagglutination  test  is  sensitive,  but  because  it  requires  large 
amounts  of  rickettsial  antigen,  it  has  remained  primarily  a  research 
tool.  The  latex  agglutination  test,  which  is  simple,  quick,  and  requires 
no  elaborate  instrumentation,  is  now  commercially  available. 

Another  promising  approach  to  diagnosis  took  advantage  of  the 
abihty  to  "label"  antibodies  with  fluorescent  or  radioactive  material 
or  with  enzymes.  To  test  for  the  presence  of  R.  rickettsii^  antibodies 
labeled  with  fluorescent  dye  are  added  to  a  patient's  serum  on  a  glass 
slide  and  allowed  to  react.  After  being  washed  to  remove  any  unat- 
tached antibodies,  the  slide  is  examined  under  an  ultraviolet  light, 
which  renders  visible  any  labeled  antibodies  attached  to  the  rickettsiae. 
If  no  rickettsiae  are  present,  all  the  labeled  antibodies  are  washed 
away,  and  no  fluorescence  is  seen.  Before  this  technique  was  adapted 
for  diagnosis  of  spotted  fever,  it  had  been  widely  used  in  research 
laboratories.  As  early  as  1950,  A.  H.  Coons  and  his  colleagues  used 
a  fluorescence  technique  to  describe  rickettsiae  in  the  human  body 
louse.  In  i960  and  1961,  Willy  Burgdorfer  and  David  B.  Lackman 
adapted  the  technique  to  identify  Rickettsia  rickettsii  in  tissues  of 
infected  ticks  and  guinea  pigs.^^  In  the  mid  1970s,  antibody  labeling 
was  employed  for  laboratory  diagnosis  of  spotted  fever.  Variations  of 
the  technique  have  produced  direct  and  indirect  immunofluorescence 


Mysteries  Explained,  Mysteries  Remaining 


tests,  a  microimmunofluorescence  test,  and  an  enzyme-linked  immu- 
noabsorbent  assay.^"^  Studies  of  the  new  tests  have  demonstrated  that 
their  sensitivity  is  significantly  greater  than  the  old  Weil-Felix  and 
complement  fixation  tests. 

In  the  late  1970s,  two  groups  reported  the  development  of  the  most 
rapid  diagnostic  test  yet  available.  A  team  from  Fort  Detrick  and  the 
University  of  Maryland  led  by  Theodore  E.  Woodw^ard  found  that  as 
early  as  the  fourth  day  of  illness,  a  skin  biopsy  of  any  suspect  rash 
could  be  tested  v^ithin  four  hours  by  the  indirect  immunofluorescence 
test.  David  H.  Walker  and  his  associates  at  the  University  of  North 
Carolina  School  of  Medicine  adapted  the  direct  fluorescent  antibody 
technique  for  the  skin  biopsy  method.  Both  techniques  w^ere  demon- 
strated useful  in  diagnosing  suspected  cases  of  spotted  fever.^^ 

Although  all  of  these  nev^  tests  promised  quicker,  more  sensitive, 
and  more  reUable  results  than  the  old  complement  fixation  test,  none 
of  them.  Walker  observed  in  a  1982  review^  paper,  could  be  relied  on 
by  the  practicing  physician  for  the  diagnosis  of  acute  spotted  fever. 
Unless  a  rash  had  already  developed  from  w^hich  a  skin  biopsy  could 
be  taken— and  many  fatal  cases  of  spotted  fever  show^ed  no  rash  in 
the  early  stages— patients  usually  lacked  sufficient  antibody  levels  for 
laboratory  tests  to  be  useful.  Just  the  previous  year,  however.  Walker 
and  his  colleagues  had  identified  eschars  in  spotted  fever  patients.  These 
small,  dark  scabs  covering  the  site  where  an  infected  tick  had  attached 
were  characteristic  of  many  rickettsial  infections,  but  they  had  been 
considered  notably  absent  in  Rocky  Mountain  spotted  fever.  Although 
eschars  in  spotted  fever  might  continue  to  be  unusual  events,  the 
researchers  noted,  their  potential  existence  could  prove  helpful  in  di- 
agnosis. In  addition  to  assisting  clinical  diagnosis,  a  biopsy  of  the 
eschar  might  reveal  the  presence  of  rickettsiae  before  the  skin  rash 
appeared. 

At  present,  rapid  diagnosis  of  Rocky  Mountain  spotted  fever  depends 
primarily  on  a  physician's  awareness  that  a  patient  might  be  at  risk 
to  contract  the  disease.  Especially  in  geographic  areas  where  spotted 
fever  is  rarely  seen,  a  medical  history  that  includes  questions  about 
recent  travel  in  areas  where  ticks  are  prevalent  may  be  the  principal 
clue.  To  alert  both  physicians  and  the  public  to  the  dangers  of  the 
disease,  a  variety  of  media  has  been  utilized  by  state  health  agencies 
in  highly  infected  areas.  In  Virginia,  for  example,  a  public  education 
program  keyed  to  the  theme  "Virginia's  Hidden  Enemy"  includes 
newspaper  articles,  television  and  radio  announcements,  brochures 
aimed  at  practicing  physicians,  and  posters  located  in  schools  and 
other  public  places. Such  efforts  are  especially  useful  to  visitors  from 


Rocky  Mountain  Spotted  Fever 


Willy  Burgdorfer  of  the  Rocky  Mountain  Laboratories  became  one  of  the 
leading  investigators  of  spotted  fever  during  its  surprising  upsurge  in  the 
1970s.  His  contributions  included  an  explanation  of  v^hy  the  disease  had 
been  limited  to  the  west  side  of  the  Bitterroot  River  and  the  discovery  of 
the  organism  that  causes  Lyme  disease— a  serendipitious  offshoot  of  spotted 
fever  research.  (Courtesy  of  the  Rocky  Mountain  Laboratories,  NIAID.) 


noninfected  areas,  who  are  often  unaware  that  a  disease  known  as 
Rocky  Mountain  spotted  fever  might  pose  a  threat  outside  the  western 
states. 

Another  widespread  misconception  about  spotted  fever  is  that  chil- 
dren are  the  only  group  likely  to  contract  it.  Having  more  contact 
through  outdoor  play  with  wooded  areas  and  with  dogs  harboring 
ticks,  children  between  the  ages  of  five  and  nine  certainly  incur  the 
largest  number  of  cases.  As  a  group  from  the  Bureau  of  Epidemiology 
of  the  Centers  for  Disease  Control  noted  in  1982,  however,  it  is  adult 
victims  between  the  ages  of  forty  and  fifty-nine  who  are  the  most  likely 
to  die,  once  infected.  Again,  the  key  to  recovery  is  rapid  diagnosis, 
and,  unfortunately,  physicians  who  treat  adults  are  less  likely  to  rec- 
ognize symptoms  as  rapidly  as  pediatricians,  most  of  whom  have  seen 
numerous  cases  among  their  patients.  "It  has  been  my  twenty-year 


Mysteries  Explained,  Mysteries  Remaining 


253 


long  experience,"  Willy  Burgdorfer  commented,  however,  "that  once 
a  physician  loses  a  patient  to  spotted  fever,  he  v^ill  not  lose  a  second 
one,  because  death  from  spotted  fever  is  an  unnecessary  loss  of  life."^^ 

Burgdorfer  had  studied  Rickettsia  rickettsii,  as  well  as  numerous 
other  organisms,  since  coming  to  the  Rocky  Mountain  Laboratory  in 
the  1950s  from  Switzerland.  In  the  early  1980s  his  research  on  one 
longstanding  mystery  relating  to  Rocky  Mountain  spotted  fever  pro- 
duced the  spin-off  solution  to  another  mystery  in  an  ancillary  field, 
the  discovery  of  the  organism  that  caused  Lyme  disease.  First  identified 
in  Old  Lyme,  Connecticut— hence  its  name— this  disease  caused  a 
characteristic  bull's-eye  rash,  followed  by  a  variety  of  symptoms,  in- 
cluding arthritis,  heart  complications,  and  neurological  disorders.  In- 
vestigators at  Yale  University,  particularly  Allan  Steere,  had  discovered 
that  Lyme  disease  responded  to  penicillin  treatment,  but  the  etiologic 
agent  remained  unidentified  until  Burgdorfer  traveled  to  New  York  to 
search  for  ticks  infected  with  R.  rickettsii  along  the  northeast  coast. 

Twenty-five  to  fifty  cases  of  spotted  fever  occurred  each  year  in  this 
area,  but  R.  rickettsii  had  never  been  isolated  from  local  ticks.  In  1979, 
Burgdorfer  joined  forces  with  Jorge  L.  Benach  of  the  New  York  State 
Department  of  Health  in  a  concerted  effort  to  solve  the  puzzle.  In 
areas  where  spotted  fever  had  been  contracted,  Benach  and  Burgdorfer 
collected  several  thousand  Dermacentor  variabilis  ticks— the  common 
dog  tick  usually  associated  with  the  disease  in  the  east.  To  test  the 
ticks,  Burgdorfer  employed  a  "hemolymph"  test  he  had  developed  in 
1970  that  allowed  quick  determination  of  the  presence  of  rickettsiae. 
One  leg  of  a  tick  was  amputated  and  a  drop  of  hemolymph  from  the 
wound  placed  on  a  microscopic  slide.  When  stained  by  the  Gimenez 
method,  rickettsiae  were  easily  visible  under  the  microscope.  Positive 
specimens  could  then  be  subjected  to  fluorescent  antibody  studies  to 
identify  the  particular  rickettsial  group  to  which  the  organisms  be- 
longed. This  technique  itself  was  a  quantum  leap  from  the  older  meth- 
ods of  injecting  tick  contents  into  guinea  pigs  and  waiting  to  see 
whether  they  developed  fever."^^ 

Of  the  thousands  of  ticks  tested,  "not  a  single  one  was  found  to 
have  R.  rickettsii^''  Burgdorfer  noted,  although  "about  15  percent  of 
them  were  infected  with  a  nonvirulent  type  [of  rickettsial,  R.  montana.'' 
Thinking  that  perhaps  they  were  investigating  the  wrong  tick,  Benach 
collected  several  hundred  ticks  of  the  species  Ixodes  dammini,  which 
were  usually  parasites  of  deer  but  were  more  numerous  in  the  area 
than  the  dog  tick.  He  sent  them  to  Burgdorfer,  who  examined  them 
at  the  RML  for  rickettsiae.  They,  too,  were  all  negative.  "But  in  two 
ticks  I  found  a  microfilaria,"  Burgdorfer  said  in  an  interview,  after 


254 


Rocky  Mountain  Spotted  Fever 


which  he  smiled  and  noted,  "Here  comes  the  serendipity."  Having 
found  the  earHer  developmental  stage  of  a  similar  microfilaria  in  Ixodes 
ticks  in  Sv^itzerland  during  a  sabbatical  year  in  1978,  Burgdorfer  began 
dissecting  the  two  ticks  very  carefully,  "tissue  by  tissue."  He  found 
no  more  microfilariae,  but  instead  he  found  spirochetes.  Burgdorfer 
knew^  that  spirochetes  had  been  considered  as  the  possible  cause  of  a 
European  disease  similar  to  Lyme  disease,  and  he  also  knew  that 
spirochetes  were  sensitive  to  penicillin,  the  drug  that  had  been  used 
successfully  to  treat  Lyme  disease  victims.  "I  put  two  and  two  together 
and  was  convinced  I  had  discovered  the  etiologic  agent  of  Lyme  dis- 
ease." By  1982  serological  and  laboratory  work  had  confirmed  his 
hunch,  and  the  organism  was  named  in  his  honor,  Borrelia  burg- 
dorferi."^^ 

Reflecting  the  circuitous  route  by  which  scientific  discovery  often 
occurs,  Burgdorfer's  research  had  produced  the  answer  to  a  problem 
totally  unrelated  to  his  initial  work.  The  existence  of  virulent  R.  rick- 
ettsii  in  New  York  ticks,  in  fact,  still  has  not  been  demonstrated.  Other 
spotted  fever  mysteries  long  ignored,  however,  have  yielded  to  intense 
study  during  the  1970s  and  1980s.  One  line  of  research  explained  the 
phenomenon  of  reactivation,  first  noted  in  1922  by  Roscoe  R.  Spencer 
and  Ralph  R.  Parker.  At  that  time  they  experienced  a  scientific  epiphany 
when  they  realized  that  the  spotted  fever  organism  was  nonvirulent 
in  flat  ticks  and  virulent  in  engorged  ticks.  Spencer's  experiments  had 
revealed  that  either  a  blood  meal  or  warming  could  produce  a  similar 
reactivation  of  virulence  in  R.  rickettsii,  but  he  was  at  a  loss  to  explain 
the  mechanism  by  which  the  process  occurred.  During  the  1950s, 
Marianna  R.  Bovarnick  and  E.  G.  Allen  demonstrated  that  metabolic 
changes  produced  by  low  temperatures  affected  the  virulence  of  typhus 
rickettsiae.  Winston  H.  Price  and  J.  H.  Gilford  further  characterized 
the  reactivation  phenomenon,  showing  that  virulent  R.  rickettsii  could 
be  made  avirulent  by  treatment  with  PABA.  This  process  could  be 
reversed,  moreover,  by  incubation  with  particular  coenzymes.  In 
1967,  Emilio  Weiss  and  his  colleagues  confirmed  these  findings  and 
showed  that  R.  rickettsii  possessed  metabolic  requirements  similar  to 
R.  prowazekii.'^'^ 

In  1982,  Stanley  F.  Hayes  and  Burgdorfer  elucidated  the  specific 
physical  characteristics  that  accompanied  the  metabolic  changes  of 
reactivation  in  R.  rickettsii.  Using  the  electron  microscope,  they  de- 
scribed two  structures  in  the  organism  that  underwent  profound  al- 
teration as  it  changed  in  virulence.  The  "microcapsular  layer"  was  an 
outer  structure  of  the  organism,  readily  identified  in  electron  micro- 
scopic examinations  of  engorged  ticks.  Around  it  was  the  "slime  layer," 


Mysteries  Explained,  Mysteries  Remaining 


2.55 


which  formed  a  "discrete  electron-lucent  zone"  around  the  organism. 
In  starved  ticks  "neither  the  microcapsular  layer  nor  slime  layer  remains 
a  discrete  entity.  Instead,  they  are  shed  and  form  stringy,  shredded, 
and  somewhat  flocculent  strands."  Incubation  at  37°C  or  feeding  of 
starved  infected  ticks  resulted  in  the  restoration  of  these  structures, 
and,  as  a  corollary,  the  pathogenicity  and  virulence  of  the  organism. 
Continuing  study  of  the  reactivation  phenomenon  may  yield  clues 
about  the  organism's  pathogenic  mechanism  and  about  why  it  does 
so  httle  damage  to  its  tick  host.^^ 

In  contrast  to  a  satisfactory  intellectual  explanation  for  this  mystery, 
the  ecology  of  Rickettsia  rickettsii— what  Ralph  R.  Parker  always 
called  the  disease's  natural  history —  remains  only  partially  understood. 
Research  in  this  area  has  been  based  on  a  conceptual  model  articulated 
in  the  1950s  by  a  Soviet  parasitologist,  E.  N.  Pavlovsky.  The  geographic 
areas  in  which  specific  infections  occurred,  Pavlovsky  suggested,  were 
characterized  by  well-defined  ecological  peculiarities  determined  by 
topography,  climate,  vegetation,  and  other  environmental  factors.  In 
such  natural  foci,  the  pathogens,  their  vectors,  and  vertebrate  hosts 
formed  a  nidus,  or  biologically  balanced  ecological  system.  Only  when 
humans  unwittingly  stumbled  into  this  system  did  the  pathogens  be- 
come a  hazard.  J.  R.  Audy  of  the  Institute  for  Medical  Research  in 
Kuala  Lumpur,  Malaya,  colorfully  summarized  Pavlovsky's  theory  at 
a  195  8  meeting  of  the  Royal  Society  of  Tropical  Medicine  and  Hygiene 
at  Manson  House  in  London.  "A  man  does  not  look  for  lion  in  a  rain 
forest,  nor  for  rhododendrons  in  a  chalk-pit,  because  it  is  known  that 
their  preferred  habitats  are  different  from  these."  Pathogenic  organisms 
similarly  prefer  different  kinds  of  environments,  and  one  principal 
difficulty  in  studying  the  biosystems  of  particular  organisms,  Audy 
maintained,  was  the  human  tendency  to  concentrate  thought  "on  clin- 
ical disease  in  man,  rather  than  on  the  pathogen  in  its  natural  envi- 
ronment." This  has  confused  the  picture  greatly,  "for  the  distribution 
of  a  pathogen  is  wider  than  that  of  disease  caused  by  it  and  the  latter 
cannot  be  understood  without  understanding  the  former  as  a  whole." 
In  an  effort  to  enhance  their  understanding  of  biosystems  inhabited 
by  rickettsiae,  Soviet  and  eastern  bloc  investigators  have  initiated  an 
active  program  of  field  research.  A  rational  method  for  controlling 
diseases  based  on  environmental  principles  is  the  long-term  goal  of 
the  work.^"^ 

Even  before  Pavlovsky  gave  voice  to  his  theory,  the  peculiarities  of 
several  rickettsial  diseases  had  already  stimulated  investigators  in  the 
United  States  to  consider  the  natural  histories  of  the  organisms.  The 
reason  that  scrub  typhus  attacked  some  troops  and  spared  others 


Rocky  Mountain  Spotted  Fever 


during  World  War  II,  for  example,  was  explained  by  its  natural  oc- 
currence in  particular  foci,  the  so-called  islands  of  infection.  Even  older 
was  the  enigma  of  why  Rocky  Mountain  spotted  fever  had  been  limited 
to  the  west  side  of  the  river  in  the  Bitterroot  Valley.  All  sorts  of  guesses 
had  been  ventured,  from  the  unwillingness  of  ground  squirrels  to  cross 
the  river  to  analyses  of  the  vegetation  on  each  bank.  In  198 1,  Willy 
Burgdorfer,  Stanley  F.  Hayes,  and  Anthony  J.  Mavros  at  the  Rocky 
Mountain  Laboratory  addressed  the  problem  anew.  Proceeding  on  the 
initial  hypothesis  that  genetic  variations  in  Dermacentor  andersoni 
ticks  on  the  east  and  west  sides  of  the  river  might  result  in  differences 
of  susceptibility  to  infection  with  R.  rickettsii,  they  collected  large 
numbers  of  ticks  from  each  area  for  study.  Burgdorfer's  hemolymph 
test  was  used  to  identify  east  side  ticks  containing  rickettsiae;  larvae 
from  those  female  ticks  showing  none  were  allowed  to  engorge  on 
male  guinea  pigs.  Surprisingly,  although  none  of  the  guinea  pigs  de- 
veloped fever,  some  of  them  showed  low  titers  of  antibodies  to  R. 
rickettsii  when  tested  a  month  later.  "This  suggested,"  the  authors 
noted  in  their  paper,  that  some  of  the  larvae  were  infected  with  "an 
ovarially-acquired  rickettsia"  that  was  not  detected  by  hemolymph 
testing."^^ 

Subsequent  dissection  confirmed  their  suspicions.  In  "large  percen- 
tages" of  the  negative  ticks— up  to  80  percent  of  those  from  some  east 
side  locations,  a  spotted  fever  group  rickettsia,  which  was  given  the 
name  East  side  agent,  was  identified  in  specific  tissues,  especially  the 
ovaries.  In  one  test,  female  ticks  from  the  east  side  were  fed  on  guinea 
pigs  infected  with  virulent  R.  rickettsii  and  allowed  to  lay  their  eggs. 
Those  females  whose  ovaries  were  heavily  infected  with  the  East  side 
agent  showed  no  R.  rickettsii  in  their  ovaries,  although  it  was  present 
in  all  other  tissues.  Their  eggs,  moreover,  contained  only  the  East  side 
agent— R.  rickettsii  had  not  been  transmitted.  This  "interference  phe- 
nomenon," by  which  the  East  side  agent  prevented  the  establishment 
of  virulent  R.  rickettsii  in  the  ovaries  of  east  side  ticks  offered  one 
explanation  of  why  spotted  fever  was  limited  to  the  west  side  of  the 
river.  "Indeed,"  wrote  the  investigators,  "it  may  provide  a  logical 
answer  to  the  questions  why  in  certain  localities  .  .  .  virulent  strains 
of  R.  rickettsii  are  rare  or  have  never  been  established.""^^ 

From  the  beginning  of  spotted  fever  investigations  in  1902,  when 
the  tick-borne  nature  of  the  disease  was  first  postulated,  investigators 
had  sought  to  understand  and  describe  its  maintenance  in  nature.  Early 
spotted  fever  investigations  were  strongly  influenced  by  work  on  other 
vector-borne  diseases  that  had  mammalian  hosts  thought  to  be  their 
natural  reservoirs.  Such  an  animal  reservoir  was  assumed  to  exist  for 


Mysteries  Explained,  Mysteries  Remaining 


^S7 


Rocky  Mountain  spotted  fever,  and  the  earliest  investigations  had 
identified  the  Columbian  ground  squirrel  and  other  small  rodents  as 
likely  candidates.  Once  Howard  Taylor  Ricketts  had  demonstrated 
that  the  spotted  fever  organism  could  be  transmitted  through  the  eggs 
of  the  female  tick  to  later  generations,  however,  the  tick  itself  was  also 
viewed  as  a  major  disease  reservoir. 

In  19 1 6,  just  after  spotted  fever  had  been  identified  in  eastern  Mon- 
tana, Ralph  R.  Parker  pubHshed  the  disturbing  finding  that  immature 
stages  of  the  spotted  fever  tick,  Dermacentor  andersoni,  fed  on  rabbits, 
a  potentially  huge  natural  reservoir  of  the  disease.  Over  the  next  three 
decades,  Parker  continued  his  research,  assisted  by  several  young  en- 
tomologists who  carried  on  the  work  after  his  death.  They  identified 
the  rabbit  tick  Haemaphysalis  leporis-palustris,  which  rarely  bit  hu- 
mans, as  a  vector  of  one  strain  of  R.  rickettsii,  and  they  carefully 
mapped  the  geographical  locale  of  this  tick  and  its  major  host,  Syl- 
vilagus  nuttallii,  more  commonly  known  as  Nuttall's  cottontail."^^  For 
several  decades  entomologist  WilHam  L.  Jellison  championed  the  the- 
ory that  cottontails  were  probably  the  major  reservoir  of  Rocky  Moun- 
tain spotted  fever  in  the  United  States.  In  1980,  however,  he  came  out 
of  retirement  to  join  a  younger  generation  of  researchers  in  reopening 
the  question.  "The  relationship  in  the  U.S.  between  cottontail  rabbits 
and  several  species  of  Dermacentor  ticks,  including  the  main  vectors 
of  the  spotted  fever  agent,  R.  rickettsii,  is  recognized,  and  the  close 
agreement  in  the  distribution  of  cottontails  to  spotted  fever  cases  in 
certain  geographic  areas  cannot  be  disputed,"  the  group  reported. 
"However,  our  observations  do  not  support  the  hypothesis  that  cot- 
tontail rabbits  are  the  primary  reservoirs  of  Rickettsia  rickettsii  in 
nature."^^ 

Small  rodents  were  also  investigated  as  potential  natural  reservoirs 
of  spotted  fever.  Early  research  by  William  Colby  Rucker,  Lunsford 
D.  Fricks,  and  S.  Burt  Wolbach  had  indicated  that  the  meadow 
"mouse"— or  more  precisely,  a  meadow  vole—Microtus  modestus  was 
not  susceptible  to  infection. In  1934,  however,  JelHson  demonstrated 
that  these  and  other  small  rodents  not  only  could  be  infected  but  also 
could  transfer  the  infection  to  feeding  nymphal  ticks.  Although  this 
research  suggested  that  rodents  might  play  a  role  in  the  maintenance 
of  the  infection  in  nature,  Jellison  was  not  able  to  recover  rickettsiae 
from  animals  in  the  wild.  Twenty  years  later,  however,  Douglas  J. 
Gould  and  Marie  L.  Miesse  at  the  Walter  Reed  Army  Medical  Center 
confirmed  Jellison's  prediction.  They  recovered  spotted  fever  group 
rickettsiae  from  the  tissues  of  a  meadow  vole,  Microtus  pennsylv aniens, 
during  a  study  in  suburban  Alexandria,  Virginia.  Their  study  did  not 


258 


Rocky  Mountain  Spotted  Fever 


indicate  the  actual  prevalence  of  spotted  fever  among  v^ild  meadow^ 
voles,  nor  did  it  determine  the  role  played  by  these  mammals  in  the 
maintenance  of  spotted  fever  in  nature.  Additional  research  on  small 
animal  reservoirs  and  their  tick  vectors  by  Willy  Burgdorfer  and  his 
colleagues  during  the  1960s  pointed  out  the  complexity  of  the  problem, 
w^hich  will  not  easily  be  solved. ^° 

In  1935,  Ralph  R.  Parker  had  also  raised  the  question  of  cycles  in 
the  occurrence  of  spotted  fever,  an  observation  that  w^ould  prove  pre- 
scient in  the  late  1960s  w^hen  the  disease  began  increasing  in  the  United 
States  for  no  identifiable  reason.  Parker's  data  on  the  yearly  incidence 
of  spotted  fever  in  seven  western  states  showed  peaks  of  incidence  in 
19 1 5,  1922,  and  1929,  which  suggested  a  seven-year  cycle.  What 
caused  this  cycle,  however,  was  not  clear.  Variations  in  the  number  of 
persons  exposed,  in  tick  abundance,  and  in  the  percentage  of  ticks 
carrying  virulent  organisms  might  all  contribute  to  such  a  phenomenon. 
Parker  also  acknowledged  that  there  were  probably  "even  more  fun- 
damental" influences  underlying  these  cycles.  As  two  examples  of  this, 
he  cited  factors  that  benefited  or  harmed  the  hosts  of  each  stage  of 
the  tick  and  meteorological  conditions  affecting  the  portions  of  the 
tick  life  cycle  spent  in  estivation  or  hibernation.  "The  possible  factors 
that  affect  the  degree  of  virulence  of  the  virus  in  ticks  in  nature,  and 
which  consequently  determine  whether  it  will  cause  frank  or  inapparent 
infections,  are  not  understood.  .  .  .  That  such  factors  are  certainly 
involved,  however,  is  shown  by  evidence"  such  as  variations  in  wild 
ticks'  ability  to  produce  recognizable  infections  in  laboratory  animals 
some  years  and  not  in  others. 

This  line  of  research  was  continued  after  World  War  II  as  funds  and 
interest  permitted.  In  1961,  for  example,  a  Virginia  health  officer, 
F.  J.  Spencer,  pubhshed  the  results  of  data  on  the  incidence  of  Rocky 
Mountain  spotted  fever  and  tularemia  in  Virginia  between  1949  and 
1958.  His  data  indicated  that  68.4  percent  of  the  588  cases  of  spotted 
fever  occurred  east  of  Virginia's  western  mountains.  Within  this  eastern 
area,  moreover,  six  counties  in  south-central  Virginia  reported  16.3 
percent  of  the  spotted  fever  cases  and  25.7  percent  of  the  tularemia 
cases.  Spencer  suggested  that  these  figures  represented  Pavlovsky's 
concept  of  the  nidality  of  disease  and  argued  that  they  might  indicate 
synergism  between  tularemia  and  spotted  fever  in  this  focal  area.^^ 

Another  study,  conducted  by  a  group  of  investigators  led  by  Verne 
F.  Newhouse  at  the  Centers  for  Disease  Control,  used  sophisticated 
statistical  analysis  to  examine  ten  geographic  and  sociologic  variables 
in  each  of  the  159  counties  of  Georgia  in  an  attempt  to  determine  how 
they  were  correlated  with  the  occurrence  of  spotted  fever.  Through 


Mysteries  Explained,  Mysteries  Remaining 


259 


techniques  known  as  principal-component  analysis  and  cluster  anal- 
ysis, the  group  identified  four  geographically  similar  areas  in  Georgia 
that  exhibited  different  incidences  of  spotted  fever.  The  disease  was 
low  in  the  south  and  in  the  "upper  north,"  moderate  in  the  central 
region,  and  high  in  the  "lower  north."  The  most  important  variables, 
they  found,  were  climate  and  geography  — factors  that  annually  en- 
hanced or  diminished  tick  populations.  Of  secondary  but  still  major 
importance,  they  discovered,  were  the  changes  wrought  during  the 
fifteen-year  period  by  humans  on  the  environment.  These  changes 
included  suburban  development  and  the  reclamation  of  wooded  land 
for  recreational  purposes. ^'^ 

Such  recent  ecological  studies  of  spotted  fever  underscore  the  earliest 
observations  about  the  disease,  that  it  is  a  place  disease,  a  disease  of 
nature.  Because  of  its  generational  transmission  in  ticks.  Rocky  Moun- 
tain spotted  fever  will  probably  never  be  eradicated.  Unlike  its  close 
relative  epidemic  typhus,  however,  spotted  fever  does  not  represent  a 
smoldering  threat  that  could  rapidly  become  a  large-scale  killer  in  time 
of  war.  A  number  of  questions  remain  unanswered,  and  neither  lab- 
oratory diagnosis  nor  prevention  is  ideally  reliable.  Nonetheless,  Rocky 
Mountain  spotted  fever  is  curable  and,  in  conjunction  with  public 
education  programs,  a  manageable  disease.  The  measures  employed 
against  spotted  fever  through  the  decades  since  it  was  first  identified 
have  reflected  both  the  facility  and  the  limitations  of  medical  research 
during  the  twentieth  century.  As  the  number  of  martyrs  to  laboratory- 
acquired  spotted  fever  suggests,  however,  this  disease  has  been  and 
remains  a  dangerous  adversary.  The  history  of  Rocky  Mountain  spot- 
ted fever  thus  stands  not  only  as  a  tribute  to  organized  inquiry  in  the 
medical  sciences  but  also  as  a  reminder  that,  because  humans  and 
microorganisms  share  the  earth's  biosystem,  vigilance  against  infec- 
tious diseases  must  continually  be  maintained. 


Abbreviations 


cc 

MSBE 

MSBE,  First  Biennial  Report 
MSBE,  Second  Biennial  Report 
MSBE,  Third  Biennial  Report 
MSBE,  Fourth  Biennial  Report 
MSBE,  Fifth  Biennial  Report 
MSBE,  Seventh  Biennial  Report 
MSBE,  Eighth  Biennial  Report 
MSBE,  Ninth  Biennial  Report 
MSBH 

MSBH  Minutes 


Correspondence  of  Robert  A.  Cooley 
during  his  tenure  as  secretary  of  the 
Montana  State  Board  of  Entomology, 
17  bound  volumes,  Montana  State 
Archives,  Helena 

Montana  State  Board  of  Entomology 

Montana  State  Board  of  Entomology, 
First  Biennial  Report,  191^—1914 
(Helena,  191 5) 

Montana  State  Board  of  Entomology, 
Second  Biemiial  Report,  191^—1916 
(Helena,  1917) 

Montana  State  Board  of  Entomology, 
Third  Biennial  Report, 
(Helena,  1919) 

Montana  State  Board  of  Entomolog>', 
Fourth  Biennial  Report,  i^i^i^zo 
(Helena,  192 1) 

Montana  State  Board  of  Entomology, 
Fifth  Biennial  Report,  i^iz—i^z^ 
(Helena,  1924) 

Montana  State  Board  of  Entomolog)', 
Seventh  Biennial  Report,  191J-1918 
(Great  Falls  [1929]) 

Montana  State  Board  of  Entomology, 
Eighth  Biennial  Report,  i^z^ip^o 
(Great  Falls  [193 1]) 

Montana  State  Board  of  Entomology, 
Ninth  Biennial  Report,  ipji-ip^z 
(Helena  [1933]) 

Montana  State  Board  of  Health 

Minutes  of  the  Montana  State  Board 
of  Health,  Montana  State  Archives, 
Helena 


261 


262 

MSBH  Records 

MSBH,  First  Biennial  Report 

MSBH,  Second  Biennial  Report 

MSBH,  Third  Biennial  Report 

MSBH,  Fourth  Biennial  Report 

MSBH,  Tenth  Biennial  Report 

NARA,  Saint  Louis 
NIAID 

MAID  files,  NIH  Historical 
Office 

NIH 

NLM 

PH-MHS,  Annual  Report  (year) 


Abbreviations 

Montana  State  Board  of  Health 
Records,  Record  Group  28,  Montana 
State  Archives,  Helena 

Montana  State  Board  of  Health,  First 
Biennial  Report  of  the  Montana  State 
Board  of  Health  from  Its  Creation 
March  ij,  ipoi  to  November  50, 
1^02  (Helena,  [1903]) 

Montana  State  Board  of  Health, 
Second  Biennial  Report  of  the 
Montana  State  Board  of  Health  from 
December  i,  1^01  to  November  30, 
1904  (Helena,  [1905]) 

Montana  State  Board  of  Health,  Third 
Biennial  Report  of  the  Montana  State 
Board  of  Health  from  December  i, 
1904  to  November  50,  1906  (Helena, 
[1907]) 

Montana  State  Board  of  Health, 
Fourth  Biennial  Report  of  the  Montana 
State  Board  of  Health  and  First 
Biennial  Report  of  the  State  Registrar 
of  Births  and  Deaths,  1907  and  1908 
(Helena,  [1909]) 

Montana  State  Board  of  Health,  Tenth 
Biennial  Report  of  the  Montana  State 
Board  of  Health  for  the  Years  1919- 
1910  (Helena,  [192.1]) 

Federal  Records  Center,  National 
Archives  and  Records  Administration, 
Saint  Louis,  Missouri 

National  Institute  of  Allergy  and 
Infectious  Diseases 

Vertical  file  of  information  on  the 
history  of  Rocky  Mountain  spotted 
fever  and  on  the  National  Institute  of 
Allergy  and  Infectious  Diseases, 
National  Institutes  of  Health  Historical 
Office,  Bethesda,  Maryland 

National  Institute(s)  of  Health 

National  Library  of  Medicine 

U.S.  Treasury  Department,  Public 
Health  Service,  Annual  Report  of  the 
Surgeon  General  of  the  United  States 
Public  Health  and  Marine  Hospital 


Abbreviations 


263 


PHS  Records 


Ricketts  Papers 


RML,  Annual  Report  (year) 

RML,  Monthly  Report, 
(month  and  year) 

RML  Research  Records 


RML  Scrapbook 
(period  indicated) 

ZEA 


Service  (Washington,  D.C.: 
Government  Printing  Office,  annual 
publication,  1902-12) 

Records  of  the  U.S.  Public  Health 
Service,  Record  Group  90,  National 
Archives  and  Records  Administration, 
Washington,  D.C. 

How^ard  Taylor  Ricketts  Papers, 
Department  of  Special  Collections, 
Joseph  Regenstein  Library,  University 
of  Chicago,  Chicago 

Rocky  Mountain  Laboratory,  Annual 
Report^  Rocky  Mountain  Laboratories, 
Hamilton,  Montana 

Monthly  reports  filed  by  the  director  of 
the  Rocky  Mountain  Laboratory  (or  its 
earlier  designations),  Montana  State 
Archives,  Helena 

Research  Records  of  the  Rocky 
Mountain  Laboratory,  Records  of  the 
National  Institutes  of  Health,  Record 
Group  443,  National  Archives  and 
Records  Administration,  Washington, 
D.C. 

Six  Scrapbooks  of  the  Rocky  Mountain 
Laboratory,  1919-49,  Rocky 
Mountain  Laboratories,  Hamilton, 
Montana 

Archives  of  the  Department  of  Zoology 
and  Entomology,  Montana  State 
University,  Renne  Library,  Bozeman 


Notes 


Chapter  One:  A  Twentieth -Century  Disease  of  Nature 

1.  James  W.  Moulder,  "The  Rickettsias,"  in  R.  E.  Buchanan  and  N.  E. 
Gibbons,  eds.,  Bergey's  Manual  of  Determinative  Bacteriology^  8th  ed.  (Bal- 
timore: Williams  &  Wilkins  Co.,  1974),  882;  S.  Stanley  Schneierson,  Atlas 
of  Diagnostic  Microbiology  (North  Chicago:  Abbott  Laboratories,  1974),  4, 
36. 

2.  Tsutsugamushi,  or  scrub  typhus,  was  known  in  the  Orient  at  least  by 
the  sixteenth  century.  Its  history  is  discussed  in  chap.  6. 

3.  W.  C.  Rucker,  "Rocky  Mountain  Spotted  Fever,"  Public  Health  Reports 
27  (I9i2):i47i. 

4.  George  T.  Harrell,  "Treatment  of  Rocky  Mountain  Spotted  Fever  with 
Antibiotics,"  Annals  of  the  New  York  Academy  of  Science  55  (i952):io27- 
42. 

5.  WilHam  D.  Tigertt,  "A  1759  Spotted  Fever  Epidemic  in  North  Carohna," 
Journal  of  the  History  of  Medicine  and  Allied  Sciences  42  (i987):296-304. 

6.  Mary  A.  Newcomb,  Four  Years'  Personal  Experience  in  the  War  (Chicago: 
H.  S.  Mills  &  Co.,  1893).  I  ^ni  grateful  to  Fredrick  Hambrecht  for  bringing 
this  reference  to  my  attention. 

7.  My  discussion  of  the  early  history  of  typhus  is  based  on  Hans  Zinsser, 
Rats,  Lice,  and  History  (Boston:  Little,  Brown  &  Co.,  1935),  and  on  John 
C.  Snyder,  "Typhus  Fever  Rickettsiae,"  in  Frank  L.  Horsfall,  Jr.,  and  Igor 
Tamm,  eds..  Viral  and  Rickettsial  Infections  of  Man,  4th  ed.  (Philadelphia: 
J.  B.  Lippincott  Co.,  1965),  1059-94. 

8.  Dale  C.  Smith,  "The  Rise  and  Fall  of  Typhomalarial  Fever:  II.  Decline 
and  Fall,"  /.  Hist.  Med.  Allied  Sci.  37  (i982):287-32i. 

9.  See,  for  example,  Erwin  H.  Ackerknecht,  Medicine  in  the  Paris  Hospital, 
1J94—1848  (Baltimore:  Johns  Hopkins  Press,  1967);  and  Erna  Lesky,  The 
Vienna  Medical  School  in  the  Nineteenth  Century  (Baltimore:  Johns  Hopkins 
University  Press,  1976). 

10.  William  Wood  Gerhard,  "On  the  Typhus  Fever,  Which  Occurred  at 
Philadelphia  in  the  Spring  and  Summer  of  1836,"  American  Journal  of  Medical 
Science  19  (1837): 289-92,  298-99,  302—3;  Dale  C.  Smith,  "Gerhard's  Dis- 
tinction between  Typhoid  and  Typhus  and  Its  Reception  in  America,  1833- 
1860,"  Bulletin  of  the  History  of  Medicine  54  (i98o):368-85. 

11.  Rudolf  Virchow,  "Report  on  the  Typhus  Epidemic  in  Upper  Silesia," 
Eng.  trans,  in  L.  J.  Rather,  ed.,  Rudolf  Virchow:  Collected  Essays  on  Public 
Health  and  Epidemiology.,  2  vols.  (Canton,  Mass.:  Science  History  Publica- 
tions, 1985),  2:205-319. 

12.  See,  for  example,  Claude  Bernard,  An  Introduction  to  Experimental 
Medicine,  trans.  Henry  C.  Greene  (New  York:  Macmillan  Co.,  1927);  Rudolf 
Virchow,  Cellular  Pathology,  trans.  Frank  Chance  (Philadelphia:  J.  B.  Lip- 
pincott Co.,  1863);  and  Robert  Hagelstein,  "The  History  of  the  Microscope," 
New  York  Microscopial  Society  Bulletin  2  (i944):i-i9. 


265 


266 


Notes  to  Pages  p-14 


Chapter  Two:  A  Blight  on  the  Bitterroot 

1.  Gretchen  Jellison,  Introduction,  in  Bitter  Root  Valley  Historical  Society, 
ed.,  Bitterroot  Trails,  2  vols.  (Darby,  Mont.:  Professional  Impressions,  1982), 
1:17.  In  recent  years  the  words  Bitter  and  Root  have  been  combined  officially. 
In  the  early  years  of  the  century,  the  rwo-word  form  was  invariably  used. 

2.  Samuel  Lloyd  Cappious,  "A  History  of  the  Bitter  Root  Valley  to  19 14," 
M.A.  thesis.  University  of  Washington,  1939,  1-2.  Curiously,  Cappious  never 
mentions  spotted  fever. 

3.  Peter  Ronan,  History  of  the  Flathead  Indians  (Minneapolis:  Ross  & 
Haines,  1890);  John  Duffy,  The  Healers:  A  History  of  American  Medicine 
(Urbana:  University  of  Illinois  Press,  1979),  2—4;  idem,  "Medicine  and  Medical 
Practices  among  Aboriginal  American  Indians,"  in  Felix  Marti-Ibanez,  ed.. 
History  of  American  Medicine:  A  Symposium  (New  York:  MD  Publications, 
1959),  15-33- 

4.  Duffy,  "Medicine  and  Medical  Practices";  Paul  C.  Phillips,  Medicine  in 
the  Making  of  Montana  (Missoula:  Montana  State  University  Press,  1962), 
i;  Ronan,  History  of  the  Flathead  Indians,  13-14;  Report  of  the  investigation 
of  Louis  B.  Wilson  and  William  M.  Chowning  in  MSBH,  First  Biennial  Report. 

5.  Reuben  G.  Thwaites,  ed..  The  Journals  of  Lewis  and  Clark,  8  vols.  (New 
York,  1905;  reprint,  New  York,  Arno  Press,  1969),  3:52-57,  5:246;  Cappious, 
"History  of  the  Bitter  Root  Valley,"  6-10;  Phyllis  Twogood,  Henry  Grant, 
and  Lena  Bell,  "History  of  Lewis  and  Clark  Expedition  in  the  Bitter  Root 
Valley,"  in  Bitter  Root  Valley  Historical  Society,  ed.,  Bitterroot  Trails  1:37- 
45;  Phillips,  Medicine  in  the  Making  of  Montana,  20-31. 

6.  L.  D.  Pricks,  "Rocky  Mountain  Spotted  Fever,"  manuscript,  file  "S.F. 
History  (Manuscript  by  Dr.  Fricks  on  R.M.S.F.),"  p.  2,  RML  Research  Records. 

7.  Ibid.,  2-3. 

8.  Monica  G.  Shannon,  "Catholicity  in  the  Bitter  Root  Valley,"  in  "The 
Bitter  Root  Valley  Illustrated,"  magazine  suppl.  to  the  Western  News,  May 
19 10,  35;  Cappious,  "History  of  the  Bitter  Root  Valley,"  54-61,  65-67; 
Ronan,  History  of  the  Flathead  Indians,  22-33,  38-41;  Phillips,  Medicine  in 
the  Making  of  Montana,  34-40. 

9.  Cappious,  "History  of  the  Bitter  Root  Valley,"  11-15,  16-17. 

10.  Weekly  Missoulian,  28  May  and  13  October,  1880,  as  cited  in  Robert 
N.  Philip,  "AJournalistic  View  of  Western  Montana,  1870-19 10:  Some  News- 
paper Items  Relevant  to  the  Development  of  the  Bitter  Root  Valley  and  the 
Occurrence  of  Rocky  Mountain  Spotted  Fever,"  manuscript,  1984,  i.  Copies 
of  this  manuscript  have  been  deposited  in  the  Ravalli  County  Historical  Mu- 
seum and  the  library  at  the  University  of  Montana. 

11.  "The  World  Famous  Valley  of  the  Bitter  Root:  Its  Early  History,  Its 
Incomparable  Resources  and  the  Men  Who  Have  Wrought  Mightily  in  Its 
Development,"  in  "The  Bitter  Root  Valley  Illustrated,"  magazine  suppl.  to  the 
Western  News,  May  1910,  7;  W.  B.  Harlan,  "Pioneer  Fruit  Growers  of  the 
Bitter  Root,"  in  ibid.,  10.  Missoula  and  Cedar  Creek  Pioneer,  24  November 
1870,  and  Weekly  Missoulian,  20  April  1883,  as  quoted  in  Philip,  "Journalistic 
View,"  I,  27. 

12.  Missoula  Pioneer,  9  December  1871,  and  Pioneer,  24  August  1872,  as 
cited  in  Philip,  "Journalistic  View,"  3;  Ronan,  History  of  the  Flathead  Indians, 
58-62;  Western  News,  20  October  1891,  as  cited  in  Philip,  "Journalistic  View," 
67. 


Notes  to  Pages  14-18 


267 


13.  See  Philip,  "Journalistic  View,"  18-68. 

14.  Ibid.,  47,  61. 

15.  Western  News,  8  April  1896,  as  cited  in  Philip,  "Journalistic  View," 
85. 

16.  Philip,  preface  to  "Journalistic  View,"  n.p. 

17.  Weekly  Missoulian,  11  August  1888,  23  and  30  October  1889,  Bitter 
Root  Bugle,  24  January,  5  June,  7  and  21  August,  4  and  11  September  1890, 
all  as  cited  in  Philip,  "Journalistic  View,"  52,  55,  60. 

18.  Phillips,  Medicine  in  the  Making  of  Montana,  268—75. 

19.  Weekly  Missoulian,  16  April  1880,  as  quoted  in  Phillips,  Medicine  in 
the  Making  of  Montana,  289-90,  n.  4. 

20.  Ibid.,  278,  290,  n.  7.  There  were  twenty-seven  reported  smallpox  cases 
in  this  epidemic. 

21.  The  diphtheria  epidemic  was  reported  in  the  Weekly  Missoulian,  6  March 
1885,  and  the  Indian  deaths  from  apparent  tuberculosis  in  the  same  paper, 
24  July  1885.  Both  are  cited  in  Philip,  "Journalistic  View,"  36. 

22.  The  figure  for  cases  reported  in  the  newspapers  was  tabulated  from 
Philip,  "Journalistic  View,"  for  each  year.  The  official  count  was  made  by 
Wilson  and  Chowning  and  is  given  in  their  report.  See  MSBH,  First  Biennial 
Report,  32-41. 

23.  Wilson  and  Chowning's  report,  MSBH,  First  Biennial  Report,  28,  30; 
Phillips,  Medicine  in  the  Making  of  Montana,  271. 

24.  Reports  of  two  spotted  fever  deaths  in  1 882  are  in  the  Weekly  Missoulian, 
10,  17,  and  24  March  1882.  On  6  July  1883  the  paper  reported  one  death 
from  spotted  fever.  See  Philip,  "Journalistic  View,"  25,  29. 

25.  Phillips,  Medicine  in  the  Making  of  Montana,  164,  167-68. 

26.  Ibid.,  278-81. 

27.  George  Rosen,  "The  Bacteriological,  Immunologic,  and  Chemothera- 
peutic  Period,  1875-1950,"  Bulletin  of  the  New  York  Academy  of  Medicine, 
second  series,  40  (June  1964)  1487-93. 

28.  Erwin  H.  Ackerknecht,  "Anticontagionism  between  1821  and  1867," 
Bull.  Hist.  Med.  22  (1948)  15 62-93. 

29.  Phillips,  Medicine  in  the  Making  of  Montana,  423,  omits  Minshall's 
practice  in  the  Bitterroot.  For  more  complete  information  on  his  career,  see 
Ravalli  Republican,  9  October  1895  and  23  March  1898,  Bitter  Root  Times, 
13  March  1896,  Western  News,  19  December  1906,  all  as  cited  in  Philip, 
"JournaHstic  View,"  83,  86,  96,  155. 

30.  An  Act  to  Increase  the  Efficiency  and  Change  the  Name  of  the  United 
States  Marine  Hospital  Service,  i  July  1902,  32  Stat.  L.  712. 

31.  MSBH,  First  Biennial  Report,  4,  8.  For  biographical  information  on 
Longeway,  see  Phillips,  Medicine  in  the  Making  of  Montana,  356,  359. 

32.  The  designations  black  fever  and  blue  disease  are  noted  in  G.  T. 
McCullough,  "Spotted  Fever,"  Medical  Sentinel  10  (July  1902):  225;  "black 
typhus  fever"  is  noted  in  several  sources,  including  the  Bitter  Root  Times,  24 
June  1893,     cited  in  Philip,  "Journalistic  View,"  75. 

33.  The  diagnosis  of  "typhoid  pneumonia  and  measles"  was  reported  in 
the  Daily  Missoulian,  11  May  1896,  as  cited  in  Philip,  "JournaHstic  View," 
86;  McCullough  noted  that  "the  new  Standard  dictionary"  and  "text  books 
of  authority"  identified  spotted  fever  as  cerebrospinal  meningitis  or  cerebro- 
spinal fever,  and  Journal  of  the  American  Medical  Association  reported  in 


z6S 


Notes  to  Pages  18—20 


1902  an  epidemic  of  spotted  fever  in  Montana  that  was  identified  as  cere- 
brospinal meningitis.  See  McCuUough,  "Spotted  Fever,"  225;  "The  'Spotted 
Fever'  Epidemic,"  JAMA  38  (1902):  13 13.  Spotted  fever  was  identified  as  a 
cognomen  for  typhus  as  well  as  for  cerebrospinal  meningitis  in  William  Osier, 
The  Principles  and  Practice  of  Medicine  (New  York:  D.  Appleton  &  Co., 
1892),  39,  9^- 

34.  McCuUough  stated  that  the  disease  was  also  known  in  Idaho  and  Alaska. 
See  his  "Spotted  Fever,"  225. 

35.  For  biographical  information  on  Wood  see  James  F.  Hammarsten,  "The 
Contributions  of  Idaho  Physicians  to  Knowledge  of  Rocky  Mountain  Spotted 
Fever,"  Transactions  of  the  American  Clinical  and  Climatological  Association 
94  (i982):28-29,  33-41. 

36.  Marshall  W.  Wood,  "Spotted  Fever  as  Reported  from  Idaho,"  U.S.  War 
Department,  Report  of  the  Surgeon  General  of  the  Army  to  the  Secretary  of 
War,  1896  (Washington,  D.C.:  Government  Printing  Office,  1896),  60. 

37.  On  Wood's  attack  of  spotted  fever,  see  Edward  E.  Maxey,  "Rocky 
Mountain  Spotted  Fever.  A  Summary  of  Progress,"  exerpts  from  speech  given 
3  August  193 1,  in  Notebook  "RMSF— Idaho— Early  History,"  Notebooks  of 
Ralph  R.  Parker  (hereafter  cited  as  R.  R.  Parker  Notebooks,  RML  Research 
Records). 

38.  Wood,  "Spotted  Fever,"  61,  63. 

39.  Edward  E.  Maxey,  "Some  Observations  on  the  So-called  Spotted  Fever 
of  Idaho,"  Medical  Sentinel  7  (October  1899)  143 3-3 8  (quotations  from  p. 
434). 

40.  Ibid.,  436.  For  additional  information  about  the  history  of  spotted  fever 
in  Idaho,  see  W.  O.  Spencer,  "Mountain  or  Spotted  Fever,  as  Seen  in  Idaho 
and  Eastern  Oregon,"  Medical  Sentinel  15  (i907):532-37;  "The  Present  Status 
of  Rocky  Mountain  Spotted  Fever  in  Idaho,"  in  "Rocky  Mountain  Spotted 
Fever,"  Montana  State  Board  of  Health  Special  Bulletin  no.  26  (i923):27- 
28;  Notebook  "RMSF— Idaho— Early  History,"  R.  R.  Parker  Notebooks, 
RML  Research  Records. 

41.  "Tick-borne  Infections  in  Colorado,"  abstract  in  JAMA  94  (1930):!  172; 
J.  M.  Braden,  "Some  Observations  on  Four  Cases  of  Spotted  Fever  Occurring 
in  Colorado,"  Colorado  Medicine  3  (i9o6):2i3— 19;  Notebook,  "RMSF— 
Colorado— Early  History  to  1929,"  R.  R.  Parker  Notebooks,  RML  Research 
Records;  Frederick  D.  Strieker,  "The  Prevalence  and  Distribution  of  Rocky 
Mountain  Spotted  Fever  in  Oregon,"  in  "Rocky  Mountain  Spotted  Fever," 
Montana  State  Board  of  Health  Special  Bulletin  no.  26  (i923):i8-20  (quo- 
tation from  p.  18);  Notebook  "RMSF— Oregon— Early  History  to  1925," 
R.  R.  Parker  Notebooks,  RML  Research  Records. 

42.  Albert  B.  Tonkin,  "Incidence  of  Rocky  Mountain  Spotted  Fever  in 
Wyoming,"  in  "Rocky  Mountain  Spotted  Fever,"  Montana  State  Board  of 
Health  Special  Bulletin  no.  26  (i923):23-27;  Notebook  "RMSF— Wyoming- 
Early  History  to  1926,"  R.  R.  Parker  Notebooks,  RML  Research  Records. 

43.  On  Washington,  see  A.  U.  Simpson,  "Rocky  Mountain  Tick  Fever  in 
the  State  of  Washington,"  in  "Rocky  Mountain  Spotted  Fever,"  Montana  State 
Board  of  Health  Special  Bulletin  no.  26  (i923):20-23.  On  California,  see 
F.  L.  Kelly,  "Rocky  Mountain  Spotted  Fever:  Its  Prevalence  and  Distribution 
in  Modoc  and  Lassen  counties,  California:  A  Preliminary  Report,"  California 
State  Journal  of  Medicine  14  (i9i6):407-9;  F.  L.  Kelly,  "Rocky  Mountain 
Spotted  Fever  in  California,"  Pub.  Health  Rep.  31  {1916)11'/ 4;  J.  G. 


Notes  to  Pages  11-24 


Gumming,  "Rocky  Mountain  Spotted  Fever  in  California,"  Journal  of  Infec- 
tious Diseases  21  (i9i7):509-i4;  Notebook,  "RMSF— California  — Early  His- 
tory to  1929,"  R.  R.  Parker  Notebooks,  RML  Research  Records.  On  Utah 
and  Nevada,  see  A.  A.  Robinson,  "Rocky  Mountain  Spotted  Fever,  w^ith  Report 
of  a  Case,"  Medical  Record  74  (i9o8):9i3-22;  "RMSF  — Utah  — Early  History 
to  193 1,"  and  "RMSF— Nevada  —  Early  History  to  1928,"  R.  R.  Parker  Note- 
books, RML  Research  Records. 

44.  Daily  Missoulian,  5  May  1901,  and  Western  News,  15  May  1901,  as 
cited  in  Philip,  "Journalistic  View,"  114. 

45.  Minutes  of  the  MSBH,  9  May  1901,  in  MSBH,  First  Biennial  Report, 
9—10;  Western  News,  15  May  1901,  and  Daily  Missoulian,  11  June  1901,  as 
cited  in  Philip,  "Journalistic  View^,"  11 4-1 5. 

46.  Daily  Missoulian,  11  June  1901,  as  cited  in  Philip,  "JournaHstic  View," 
115- 

47.  Western  News,  17  April  1901,  as  cited  in  Philip,  "JournaHstic  View," 
115- 

48.  Western  News,  22  May  1901,  as  cited  in  ibid.  The  physician  was  James 
William  Howard. 

49.  Edward  Burrows,  letter  to  the  editor  of  the  Western  News,  5  June  1901, 
clipping  in  RML  Scrapbook  "1919-1931";  also  cited  in  Philip,  "Journalistic 
View,"  115. 

50.  Report  of  Louis  B.  Wilson  and  William  M.  Chowning  in  MSBH,  First 
Biennial  Report,  36. 

Chapter  Three:  The  Beginning  of  Scientific  Investigations 

1.  Minutes  of  the  meeting  on  4  February  1902,  of  the  MSBH  in  MSBH, 
First  Biennial  Report,  13;  Northwest  Tribune,  11  April  1902,  as  cited  in  Philip, 
"JournaHstic  View"  (see  chap.  2,  n.  10),  124. 

2.  Western  News,  30  April  1902,  as  cited  in  Philip,  "Journalistic  View," 
121.  Two  local  physicians  presented  clinical  papers  on  spotted  fever  at  the 
meeting  of  the  Montana  Medical  Association  in  Anaconda  on  23  May  1902. 
George  T.  McCullough's  paper  "Spotted  Fever"  was  published  in  the  Medical 
Sentinel  (see  chap.  2,  n.  32).  Russell  Gwinn's  paper  was  not  published  in  a 
medical  periodical. 

3.  Daily  Missoulian,  2  May  1902,  as  cited  in  Philip,  "Journalistic  View," 
121. 

4.  Esther  Gaskins  Price,  Fighting  Spotted  Fever  in  the  Rockies  (Helena: 
Naegele  Printing  Co.,  1948),  16-19,  states  that  Strain  suggested  the  significance 
of  the  tick  to  Longeway  during  a  trip  to  the  Bitterroot  in  1901.  No  report  of 
a  1 90 1  visit  appears  in  contemporary  newspapers,  but  several  obituaries  of 
Strain  repeat  the  story  and  give  1901  as  the  date.  See  "Dr.  Earle  Strain, 
Discoverer  of  Relationship  between  Wood  Ticks,  Spotted  Fever,  Dies,"  "Dr. 
Earle  Strain  Dies  in  Great  FaHs,"  and  "Death  Takes  Expert  on  Spotted  Fever," 
clippings  dated  1953  in  Scrapbook  "1942-  ,"  RML  Scrapbooks.  The  MSBH, 
First  Biennial  Report,  25,  records  Strain's  1902  visit  to  the  vaUey.  Other 
documentation  of  the  1902  visit  is  in  Daily  Missoulian,  6  May  1902,  as  cited 
in  Philip,  "JournaHstic  View,"  121;  Charles  WardeH  Stiles,  "A  Zoological 
Investigation  into  the  Cause,  Transmission,  and  Source  of  Rocky  Mountain 
'Spotted  Fever,'  "  U.S.  Hygienic  Laboratory  Bulletin  no.  20  (1905),  17. 


270 


Notes  to  Pages  24—^0 


5.  Daily  Missoulian,  3,  6,  8,  9,  and  10  May,  Western  News,  7,  14,  21  May 
1902,  as  cited  in  Philip,  "Journalistic  View,"  1 21-122. 

6.  For  biographical  information  on  Wilson  see  Samuel  F.  Haines  and  Clark 
W.  Nelson's  sketch  of  him  in  the  Dictionary  of  American  Biography,  20  vols., 
6  supplements,  (New  York:  Charles  Scribner's  Sons,  1932-80),  suppl.  3 
(i973):83i-33  (hereafter  cited  as  DAB).  Wilson's  papers,  which  are  at  the 
Mayo  Clinic,  unfortunately  do  not  include  manuscript  materials  relating  to 
his  spotted  fever  work. 

7.  Frank  F.  Wesbrook,  Louis  B.  Wilson,  and  O.  McDaniel,  "Varieties  of 
Bacillus  Diphtheria,"  Transactions  of  the  Association  of  American  Physicians 
15  (i90o):i98— 223.  For  biographical  information  on  Wesbrook  see  H.  E. 
Robertson's  sketch  of  him,  DAB  20  {19^6):}— 4.  For  biographical  information 
on  Mallory,  see  Shields  Warren's  sketch  of  him,  ibid.,  suppl.  3  (i973):502- 
3- 

8.  Biographical  information  on  Chowning  was  kindly  supplied  by  the  Library 
and  Information  Management  Section  of  the  AMA.  Because  Chowning's  li- 
cense was  revoked  in  1936  following  his  conviction  for  "the  crime  of  abortion," 
JAMA  did  not  pubHsh  an  obituary. 

9.  Western  News,  21  May  1902,  as  cited  in  Philip,  "Journalistic  View," 
122;  Louis  B.  Wilson  and  William  M.  Chowning,  "Studies  in  Pyroplasmosis 
Hominis  ('Spotted  Fever'  or  'Tick  Fever'  of  the  Rocky  Mountains),"  Journal 
of  Infectious  Diseases  1  (i904):3i— 33;  MSBH,  First  Biennial  Report,  26—27. 

10.  MSBH,  First  Biennial  Report,  26;  Wilson  and  Chowning,  "Studies  in 
Pyroplasmosis  Hominis,"  41-42. 

11.  MSBH,  First  Biennial  Report,  29;  see  also  case  records,  ibid.,  32-41. 

12.  Wilbur  Catlin,  a  local  civil  engineer  and  draftsman,  prepared  the  dis- 
tribution maps  for  Wilson  and  Chowning.  See  Western  News,  25  June  1902, 
as  cited  in  Philip,  "Journalistic  View,"  124.  On  the  foci  of  spotted  fever  outside 
the  Bitterroot,  see  Wilson  and  Chowning,  "Studies  in  Pyroplasmosis  Hominis," 
34. 

13.  Percy  M.  Ashburn,  "Piroplasmosis  Hominis  (?)  — Spotted  Fever  of  Mon- 
tana," Lancet-Clinic,  n.s.  54  (1905)1481-94  (quotation  from  p.  492). 

14.  MSBH,  First  Biennial  Report,  42-44. 

15.  Mortality  figures  computed  by  the  author  from  Wilson  and  Chowning's 
tables,  ibid.,  32-41.  Counts  and  computation  by  the  author  based  on  cases 
cited  in  Philip,  "Journalistic  View,"  82-83,  86,  90—91,  95,  101-2,  107-8, 
116-17,  124-25. 

16.  MSBH,  First  Biennial  Report,  27;  Wilson  and  Chowning,  "Studies  in 
Pyroplasmosis  Hominis,"  43-44. 

17.  Walter  Reed,  Victor  C.  Vaughn,  and  Edward  O.  Shakespeare,  Report 
on  the  Origin  and  Spread  of  Typhoid  Fever  in  U.S.  Military  Camps  during 
the  Spanish  War  of  1898  (Washington,  D.C.:  Government  Printing  Office, 
1904);  M.  A.  Veeder,  "Flies  as  Spreaders  of  Disease  in  Camps,"  Medical 
Record,  17  September  1898,  429-30;  William  B.  Bean,  Walter  Reed:  A  Bi- 
ography (Charlottesville:  University  Press  of  Virginia,  1982),  87-91;  Edward 
F.  Keuchel,  "Chemicals  and  Meat:  The  Embalmed  Beef  Scandal  of  the  Spanish- 
American  War,"  Bull.  Hist.  Med.  48  (1974): 249-64. 

18.  For  surveys  of  scientific  developments  in  parasitology,  see  William  D. 
Foster,  A  History  of  Parasitology  (Edinburgh:  E.  &  S.  Livingstone,  1965); 
Jean  Theodorides,  "Les  Grandes  Etapes  de  la  parasitologie,"  Clio  Medica  i 
(1966):  129-45,  185-208.  For  a  short  survey  of  social  and  economic  factors 


Notes  to  Pages 


271 


in  the  professionalization  of  parasitology,  see  Michael  Worboys,  "The  Emer- 
gence and  Early  Development  of  Parasitology,"  in  Kenneth  S.  Warren  and 
John  Z.  Bowers,  eds.,  Parasitology:  A  Global  Perspective  (New  York:  Springer- 
Verlag,  1983),  1-18. 

19.  Patrick  Manson,  "On  the  Development  of  Filaria  sanguinis  hominis, 
and  on  the  Mosquito  Considered  as  a  Nurse,"  Journal  of  the  Linnean  Society 
14  (i878):304-ii.  This  worm  was  later  renamed  Wucheria  bancrofti. 

20.  L.  O.  Howard,  "A  Fifty  Year  Sketch  History  of  Medical  Entomology 
and  Its  Relation  to  Public  Health,"  in  Mazyck  P.  Ravenel,  ed.,  A  Half  Century 
of  Public  Health  (New  York:  American  PubHc  Health  Association,  1921),  413; 
H.  Harold  Scott,  A  History  of  Tropical  Medicine,  1  vols.  (London:  Edward 
Arnold,  1939),  2:1086-90. 

21.  Theobald  Smith  and  F.  L.  Kilbourne,  "Investigations  into  the  Nature, 
Causation,  and  Prevention  of  Texas  or  Southern  Cattle  Fever,"  U.S.  Department 
of  Agriculture,  Bureau  of  Animal  Industry  Bulletin  no.  i  (1893);  Tamara  Miner 
Haygood,  "Cows,  Ticks,  and  Disease:  A  Medical  Interpretation  of  the  Southern 
Cattle  Industry," /owm<3/  of  Southern  History  52  (i986):55i-64. 

22.  Koch's  postulates  were  articulated  in  his  paper  demonstrating  the  eti- 
ology of  tuberculosis.  He  stated:  "It  was  necessary  to  isolate  the  bacilli  from 
the  body,  to  grow  them  in  pure  culture  until  they  were  freed  from  any  disease- 
product  of  the  animal  organism  which  might  adhere  to  them;  and,  by  ad- 
ministering the  isolated  bacilli  to  animals,  to  reproduce  the  same  morbid 
condition  which,  as  known,  is  obtained  by  inoculation  with  spontaneously 
developed  tuberculous  material."  See  Robert  Koch,  "Die  Aetiologie  der  Tuber- 
culose,"  Berliner  Klinische  Wochenschrift  19  (1882): 221-30;  hereafter  cited 
as  Berl.  klin.  Wchnschr.  An  English  translation  of  this  paper  is  in  idem.  The 
Aetiology  of  Tuberculosis,  trans.  Dr.  and  Mrs.  Max  Pinner  (New  York:  Na- 
tional Tuberculosis  Association,  1922)  (quotation  from  p.  31).  Lester  S.  King 
has  pointed  out  that  even  for  bacterial  diseases,  the  postulates  had  to  be 
understood  as  a  method  of  elucidating  a  known  disease  process,  not  as  a  means 
of  defining  disease.  See  King,  "Dr.  Koch's  Postulates,"  /.  Hist.  Med.  Allied 
Sci.  7  (i952):350-6i. 

23.  Sally  Smith  Hughes,  The  Virus:  A  History  of  the  Concept  (New  York: 
Science  History  Publications,  1977),  12,  17—21.  Evidence  of  the  assumption 
that  yellow  fever  was  a  protozoan  disease  may  be  seen  in  Herman  B.  Parker, 
George  E.  Beyer,  and  O.  L.  Pothier,  "Report  of  Working  Party  No.  1,  Yellow 
Fever  Institute:  A  Study  of  the  Etiology  of  Yellow  Fever,"  U.S.  Public  Health 
and  Marine  Hospital  Service  Yellow  Fever  Institute  Bulletin  no.  13  (1903), 
esp.  28-3  2;  Milton  J.  Rosenau,  Herman  B.  Parker,  Edward  Francis,  and  George 
E.  Beyer,  "Report  of  Working  Party  No.  2,  Yellow  Fever  Institute:  Experimental 
Studies  in  Yellow  Fever  and  Malaria  at  Vera  Cruz,  Mexico,"  in  ibid.  no.  14 
(1905);  Milton  J.  Rosenau  and  Joseph  Goldberger,  "Report  of  Working  Party 
No.  3,  Yellow  Fever  Institute:  Attempts  to  Grow  the  Yellow  Fever  Parasite; 
the  Hereditary  Transmission  of  the  Yellow  Fever  Parasite  in  the  Mosquito," 
in  ibid.  no.  15  (1906);  Joseph  Goldberger,  "Yellow  Fever:  Etiology,  Symptoms, 
and  Diagnosis,"  in  ibid.  no.  16  (1907),  8-9. 

24.  Hughes,  The  Virus,  61—73. 

25.  Victoria  A.  Harden,  "Rocky  Mountain  Spotted  Fever  Research  and  the 
Development  of  the  Insect  Vector  Theory,  1900-19 30,"  Bull.  Hist.  Med.  59 
(i985):45i-52;  George  Henry  Falkiner  Nuttall,  "On  the  Role  of  Insects, 
Arachnids,  and  Myriapods  as  Carriers  in  the  Spread  of  Bacterial  and  Parasitic 


272 


Notes  to  Pages  32.-^6 


Diseases  of  Man  and  Animals:  A  Critical  and  Historical  Study," /o^ws  Hopkins 
Hospital  Reports  8  (i899):43-49,  71-75. 

26.  For  examples  of  the  association  between  ticks  and  blood  poisoning,  see 
Bitter  Root  Times,  12  June  1896,  as  cited  in  Philip,  "Journalistic  View,"  86. 

27.  Wilson  and  Chowning,  "Studies  in  Pyroplasmosis  Hominis,"  44-45. 
See  also  L.  B,  Wilson  and  W  M.  Chowning,  "The  Hematozoon  of  the  So- 
called  'Spotted  Fever'  of  the  Rocky  Mountains,"  Northwest  Lancet  22 
(i902):440-42. 

28.  Western  News,  11  June  1902,  as  cited  in  Philip,  "Journalistic  View," 
123. 

29.  Wilson  and  Chowning,  "Studies  in  Pyroplasmosis  Hominis,"  47-48. 

30.  MSBH,  First  Biennial  Report,  82. 

31.  J.  O.  Cobb,  "The  So-called  'Spotted  Fever'  of  the  Rocky  Mountains  — 
A  New  Disease  in  the  Bitter  Root  Valley,  Mont.,"  Pub.  Health  Rep.  17 
(i902):i869.  In  1902  the  ground  squirrel  was  known  as  Spermophilus  colum- 
bianus. 

32.  MSBH,  First  Biennial  Report,  83. 

33.  Charles  Wardell  Stiles,  "Zoological  Pitfalls  for  the  Pathologist,"  Pro- 
ceedings of  the  New  York  Pathological  Society,  1905,  16. 

34.  Northwest  Tribune,  4  July  1902,  as  cited  in  Philip,  "Journalistic  View," 
123. 

35.  Sundry  Civil  Appropriations  Act,  3  March  1901,  31  Stat.  L.  1137.  On 
the  history  of  federal  medical  research  policy,  see  Victoria  A.  Harden,  Inventing 
the  NIH:  Federal  Biomedical  Research  Policy,  i88j—i^^y  (Baltimore:  Johns 
Hopkins  University  Press,  1986),  chs.  1—2;  Cobb,  "The  So-called  'Spotted 
Fever,'  "  1868. 

36.  For  biographical  information  on  Cobb  see  his  personnel  file.  Record 
Group  090-78,  Accession  no.  0001,  Agency  Box  no.  OF,  Records  Center 
Location  no.  FU#i 34867  through  FU#i 34992,  box  #  22,  NARA,  Saint 
Louis;  Cobb,  "The  So-Called  'Spotted  Fever,'  "  1868,  1870;  Wilson  and 
Chowning,  "The  So-called  'Spotted  Fever'  of  the  Rocky  Mountains:  A  Pre- 
liminary Report  to  the  Montana  State  Board  of  Health," /AMA  39  (1902):  131- 
36. 

37.  MSBH,  First  Biennial  Report,  13. 

38.  Ravalli  Republican,  24  April  1903,  and  Daily  Missoulian,  16  April 
1903,  as  cited  in  Philip,  "Journahstic  View,"  130. 

39.  For  biographical  information  on  Anderson,  see  Ralph  C.  Williams,  The 
United  States  Public  Health  Service,  1798-19^0  (Washington,  D.C.:  Com- 
missioned Officers  Association,  195 1),  251-52;  Paul  F.  Clark,  Pioneer  Mi- 
crobiologists of  America  (Madison:  University  of  Wisconsin  Press,  1961),  211; 
Anderson's  personnel  file,  Record  Group  090-78,  Accession  no.  0001,  Agency 
Box  no.  OF,  Records  Center  Location  no.  FU#  134867  through  FU#i34992, 
Box  #  3,  NARA,  Saint  Louis. 

40.  John  F.  Anderson,  "Spotted  Fever  (Tick  Fever)  of  the  Rocky  Mountains: 
A  New  Disease,"  U.S.  Hygienic  Laboratory  Bulletin  no.  14  (1903):  7,  10,  21 
(quotation  from  p.  10);  Wilson  and  Chowning,  "Studies  in  Pyroplasmosis 
Hominis,"  32;  Daily  Missoulian,  21  May  1903,  as  cited  in  Philip,  "JournaHstic 
View,"  130. 

41.  See  Anderson,  "Spotted  Fever."  This  report  also  appeared  in  MSBH, 
Second  Biennial  Report,  123-58;  and  in  summary  form  with  the  same  title. 


Notes  to  Pages  37-40 


273 


"Spotted  Fever  (Tick  Fever)  of  the  Rocky  Mountains:  A  New  Disease,"  in 
American  Medicine  6  (1903): 506-8. 

42.  Stiles,  "Zoological  Investigation,"  25;  see  also  Stiles's  discussion  of  the 
infectivity  of  Firoplasma  in  idem,  "Zoological  Pitfalls,"  18. 

43.  Ashburn,  "Piroplasmosis  Hominis  (?),"  492. 

44.  Western  News,  6  May  1903,  as  cited  in  Philip,  "Journalistic  View^," 
129. 

45.  Western  News,  20  April  1904,  as  cited  in  Philip,  "Journalistic  View," 
136. 

46.  Stevensville  Register,  18  May  1904,  and  Ravalli  Republican,  29  April 
1904,  as  cited  in  Philip,  "Journalistic  View,"  137. 

47.  Northwest  Tribune,  6  May  1904,  as  cited  in  Philip,  "Journalistic  View," 
137. 

48.  Western  News,  6  May  1903,  as  cited  in  Philip,  "Journalistic  View," 
129. 

49.  Western  News,  20  May  1903,  and  Ravalli  Republican,  17  June  1904, 
as  cited  in  Philip,  "Journalistic  View,"  129,  138. 

50.  Elsie  McCormick,  "Death  in  a  Hard  Shell,"  Saturday  Evening  Post,  15 
November  1941,  24ff.  (quotation  from  p.  47);  advertisement  in  the  Daily 
Missoulian,  20  June  1902,  as  cited  in  Philip,  "Journalistic  View,"  125. 

51.  Stevensville  Register,  15  June  1904,  as  cited  in  Philip,  "Journalistic 
View,"  138.  For  a  survey  of  the  history  of  quackery  and  patent  medicines 
before  the  passage  of  the  1906  Pure  Food  and  Drugs  Act,  see  James  Harvey 
Young,  The  Toadstool  Millionaires:  A  Social  History  of  Patent  Medicines  in 
America  before  Federal  Regulation  (Princeton,  N.J.:  Princeton  University  Press, 
1961);  idem.  Pure  Pood:  Securing  the  Federal  Food  and  Drug  Act  of  1906 
(Princeton,  NJ.:  Princeton  University  Press,  1989). 

52.  Anderson,  "Spotted  Fever,"  40;  MSBH,  Second  Biennial  Report,  156; 
Anderson,  summary  version  of  "Spotted  Fever,"  American  Medicine  6  (1903): 
508. 

53.  See,  for  example,  an  instance  reported  in  the  Daily  Missoulian,  21  April 
and  24  May  1903,  as  cited  in  Philip,  "Journalistic  View,"  132. 

54.  MSBH,  Second  Biennial  Report,  6—7. 

55.  For  biographical  information  on  Tuttle,  see  his  obituary  in  Montana 
Record  Herald  (Helena),  9  July  1942. 

56.  During  his  first  three  months  in  office,  Tuttle  reinstated  a  three-week 
quarantine  for  measles,  threatened  county  and  local  state  health  officers  with 
lawsuits  if  they  failed  to  report  births,  deaths,  and  infectious  diseases,  and 
initiated  publication  of  the  Montana  Health  Bulletin.  See  MSBH,  Second 
Biennial  Report,  8-13. 

57.  Ibid.,  9,  44-45. 

58.  There  are  many  biographical  articles  on  Stiles,  including  James  H. 
Cassedy's  sketch  of  him,  DAB,  suppl.  3  (i903):737— 39;  and  an  autobiograph- 
ical article,  "Early  History,  in  Part  Esoteric,  of  the  Hookworm  (Uncinariasis) 
Campaign  in  Our  Southern  U.S.,"  Journal  of  Parasitology  25  (i939):283- 
308.  For  accounts  of  Stiles's  work  with  hookworm,  see  Stiles,  "Early  History"; 
James  H.  Cassedy,  "The  'Germ  of  Laziness'  in  the  South,  1900— 191 5:  Charles 
Wardell  Stiles  and  the  Progressive  Paradox,"  Bull.  Hist.  Med.  45  (1971):! 59- 
69;  John  Ettling,  The  Germ  of  Laziness:  Rockefeller  Philanthropy  and  Public 
Policy  in  the  New  South  (Cambridge,  Mass.:  Harvard  University  Press,  198 1). 


^74 


Notes  to  Pages  40-46 


59.  Stiles,  "Zoological  Investigation,"  10. 

60.  Charles  Wardell  Stiles,  "Insects  as  Disseminators  of  Disease,"  Virginia 
Medical  Semi-Monthly  6  (i90i):53-58  (quotation  from  p.  54).  Stiles's  italics. 

61.  Stiles,  "Zoological  Investigation,"  11;  PH-MHS,  Annual  Report,  1904, 
362. 

62.  Stiles,  "Zoological  Pitfalls,"  11-12. 

63.  Stiles,  "Zoological  Investigation,"  7,  19;  PH-MHS,  Annual  Report^ 
1904,  362-63. 

64.  Charles  F.  Craig,  "The  Relation  of  the  So-called  Piroplasma  Hominis 
and  Certain  Degenerative  Changes  in  the  Erythrocytes,"  American  Medicine 
8  (i904):ioi6.  For  biographical  information  on  Craig,  who  from  19 18  to 
1920  served  as  curator  of  the  Army  Medical  Museum,  see  Robert  S.  Henry, 
The  Armed  Forces  Institute  of  Pathology:  Its  First  Century,  1861-1961  (Wash- 
ington, D.C.:  Office  of  the  Surgeon  General  of  the  Army,  1964),  189;  "Charles 
F.  Craig,"  in  American  Men  of  Science^  5th  ed.,  ed.  J.  McKeen  Cattell  and 
Jacques  Cattell  (New  York:  Science  Press,  1933),  239.  In  a  personal  com- 
munication to  the  author,  16  February  1988,  Robert  N.  Philip  suggested  that 
Wilson  and  Chowning's  observations  could  have  been  affected  if  their  patients' 
blood  were  infected  with  Colorado  tick  fever  virus,  also  present  in  the  Bit- 
terroot,  although  unknown  at  that  time. 

65.  Stiles,  "Zoological  Investigation,"  29-30. 

66.  Ibid.,  8,  49,  65. 

67.  Ibid.,  20.  Ashburn  likewise  believed  that  if  no  protozoan  organism  were 
found  in  the  blood,  "the  tick  and  gopher  hypothesis  would  seem  to  die  of 
inanition,  as  it  was  merely  a  hypothesis  advanced  to  account  for  the  protozoon 
infection."  See  Ashburn,  "Piroplasmosis  Hominis  (?),"  491.  The  spelling  of 
the  Latin  words  protozoan  and  protozoon  changes  according  to  the  word's 
grammatical  use  in  the  sentence. 

68.  Stiles,  "Zoological  Investigation,"  10. 

69.  Ibid.,  44;  Ashburn,  "Piroplasmosis  Hominis  (?),"  483-85. 

70.  Stiles,  "Zoological  Investigation,"  23. 

71.  Ibid.,  32,  35. 

72.  PH-MHS,  Annual  Report,  1904,  363.  Stiles's  summary  report  also 
appeared  in  MSBH,  Second  Biennial  Report,  160-62  (quotation  from  p.  162). 

73.  Price,  Fighting  Spotted  Fever,  34-36. 

74.  Cassedy,  "  'Germ  of  Laziness,'  "  161;  James  H.  Cassedy,  "Applied 
Microscopy  and  American  Pork  Diplomacy:  Charles  Wardell  Stiles  in  Ger- 
many, 1898-1899,"  Isis  62  (i97i):5-20. 

75.  Stiles,  "Zoological  Pitfalls,"  20. 

76.  Stiles  noted  the  lack  of  any  such  experiment,  ibid.,  15. 

77.  Rankin's  death  was  reported  in  the  Daily  Missoulian,  4  May  1904.  His 
and  other  cases  of  spotted  fever  in  1904  are  cited  in  Philip,  "Journalistic  View," 
137-38. 

78.  Percy  M.  Ashburn,  "A  Suggestion  as  to  the  Treatment  of  the  'Spotted 
Fever'  of  Montana,"  Lancet-Clinic,  n.s.  54  (i905):579-84  (quotation  from 
P-  579)- 

79.  On  hydrotherapy  see  Marshall  Scott  Legan,  "Hydropathy  in  America: 
A  Nineteenth  Century  Panacea,"  Bull.  Hist.  Med.  45  (1971):  267-80;  John 
Harvey  Kellogg,  Rational  Hydrotherapy:  A  Manual  of  the  Physiological  and 
Therapeutic  Effects  of  Hydriatic  Procedures,  and  the  Technique  of  Their  Ap- 


Notes  to  Pages  46-^0 


^75 


plication  in  the  Treatment  of  Disease,  id  ed.  (Philadelphia:  F.  A.  Davis  Co., 
1903);  Simon  Baruch,  Principles  and  Practice  of  Hydrotherapy  (London:  Bail- 
liere,  Tindall  &  Co.,  1900).  Osier's  recommendation  is  in  Principles  and 
Practice  of  Medicine,  43. 

80.  Ashburn,  "Suggestion  as  to  the  Treatment,"  583,  581;  Robert  N.  Philip, 
personal  communication  to  the  author,  16  February  1988. 

81.  "Spotted  Fever," /AMA  44  (i905):i686. 

Chapter  Four:  Dr.  Ricketts's  Discoveries 

1.  See,  for  example,  references  to  such  changes  in  Western  News,  3  July 
1907, 1  July  1908,  and  27  July  and  9  September  1910,  and  Ravalli  Republican, 
26  March  1909,  all  cited  in  Philip,  "Journalistic  View^"  (see  chap.  2,  n.  10), 
158-59,  165,  176,  180. 

2.  MSBH,  Second  Biennial  Report,  66,  58,  67-68. 

3.  Robert  William  Hadlow,  "The  Big  Ditch  and  the  Mcintosh  Red:  Early 
Boosterism  in  Montana's  Bitter  Root  Valley,"  Pacific  Northwest  Forum  8  (Fall 
i983):2-i3;  Western  News,  30  October  1907,  as  cited  in  Philip,  "Journalistic 
View,"  157. 

4.  Philip  identified  the  following  cases  and  deaths  from  spotted  fever  in  this 
period  — 1904:  14  cases,  9  deaths;  1905:  10  cases,  8  deaths;  1906:  14  cases, 
II  deaths;  1907,  6  cases,  6  deaths;  1908:  10  cases,  4  deaths;  1909,  10  cases, 
8  deaths;  19 10:  8  cases,  8  deaths.  See  "Journalistic  View,"  137-38,  146-47, 
154-55,  i^ij  167-68,  176,  180.  His  figures  for  1909  include  four  fatal  cases 
in  Northern  Pacific  Railroad  workers  that  were  never  reported  in  the  press. 
On  the  creation  of  the  Montana  Bureau  of  Vital  Statistics  and  registration  of 
births  and  deaths,  see  Daily  Missoulian,  30  May  1907,  as  cited  in  Philip, 
"JournaHstic  View,"  156. 

5.  Wyman  to  the  Secretary  of  the  Treasury,  19  April  1905,  file  1266,  box 
119,  Central  File,  1 897-1923,  PHS  Records.  For  biographical  information  on 
Francis  see  American  Men  of  Science,  5th  ed.  (see  chap.  3,  n.  64),  378;  WilHams, 
United  States  Public  Health  Service  (see  chap.  3,  n.  39),  190—92;  and  Clark, 
Pioneer  Microbiologists  (see  chap.  3,  n.  39),  62,  296—97. 

6.  Daily  Missoulian,  11  June  1905,  as  cited  in  Philip,  "Journalistic  View," 
146.  Francis's  investigation  was  mentioned  in  the  1905  and  1906  annual 
reports  of  the  Service,  but  no  report  of  substance  was  ever  published.  See  PH- 
MHS,  Annual  Report,  1905,  211;  and  1906,  219. 

7.  Stiles,  "Zoological  Pitfalls"  (see  chap.  3,  n.  33).  The  observer  was  S.  Burt 
Wolbach,  whose  comment  was  pubHshed  in  "Studies  on  Rocky  Mountain 
Spotted  Yevev,''  Journal  of  Medical  Research  41  (i9i9):i-i97  (quotation  from 
p.  9). 

8.  Chowning  to  Ricketts,  15  March  1906;  and  Ricketts  to  Chowning,  17 
March  1905  (letter  misdated;  should  be  1906),  box  8,  folder  9,  Ricketts  Papers. 

9.  Chowning  to  Ricketts,  15  March  1906,  box  8,  folder  9,  Ricketts  Papers; 
Lucien  P.  McCalla,  "Direct  Transmission  from  Man  to  Man  of  the  Rocky 
Mountain  Spotted  (Tick)  Fever,"  Medical  Sentinel  16  (i9o8):87-88.  For  bi- 
ographical information  on  McCalla  see  Hammarsten,  "Contributions  of  Idaho 
Physicians"  (see  chap.  2,  n.  35),  31-33. 

10.  Howard  Taylor  Ricketts,  Infection,  Immunity,  and  Serum  Therapy  (Chi- 
cago: American  Medical  Association,  1906).  For  biographical  information  on 


276 


Notes  to  Pages  51-54 


Ricketts,  see  Pierce  C.  Mullen's  sketch  of  him  in  Charles  Coulston  Gillispie, 
ed.,  Dictionary  of  Scientific  Biography,  16  vols.  (New  York:  Charles  Scribner's 
Sons,  1970-80),  II  (i975):442-43;  William  K.  Beatty  and  Virginia  L.  Beatty, 
"Howard  Taylor  Ricketts— Imaginative  Investigator,"  Proceedings  of  the  In- 
stitute of  Medicine  of  Chicago  34  ( 198 1)  146-48;  Ludvig  Hektoen's  memorial 
address  on  Ricketts,  in  Howard  T.  Ricketts,  Contributions  to  Medical  Science 
by  Howard  Taylor  Ricketts,  iSjo-i^io  (Chicago:  University  of  Chicago  Press, 
1911),  3-7;  H.  Gideon  Wells's  sketch  of  him,  DAB  (see  chap.  3,  n.  6),  suppl. 
I  (1944),  628—29;  Clark,  Pioneer  Microbiologists,  285—91;  obituary, /AMA 
54  (i9io):i640.  No  book-length  biography  of  Ricketts  has  yet  been  written. 
On  Ricketts's  study  with  Henry  B.  Ward,  see  Edwin  F.  Hirsch,  "The  Insect 
Vector  as  Transmitter  of  Disease,"  Proceedings  of  the  Institute  of  Medicine 
of  Chicago  27  (i969):294.  On  medical  education  during  this  period,  see  the 
classic  report  of  Abraham  Flexner,  Medical  Education  in  the  United  States 
and  Canada  (New  York:  Carnegie  Foundation,  19 10).  An  excellent  recent 
study  is  Kenneth  M.  Ludmerer,  Learning  to  Heal:  The  Development  of  Amer- 
ican Medical  Education  (New  York:  Basic  Books,  1985). 

11.  Spottswood  to  Ricketts,  10  April  1906;  and  Ricketts  to  Tuttle,  29  June 
1906,  box  8,  folder  9,  Ricketts  Papers;  Ricketts's  report  in  MSBH,  Third 
Biennial  Report,  22—23;  William  M.  Chowning,  "Rocky  Mountain  Spotted 
Fever:  Preliminary  Reports,"  Journal  of  the  Minnesota  State  Medical  Asso- 
ciation and  the  Northwest  Lancet  27  (1907) :ioi. 

12.  Williams,  United  States  Public  Health  Service,  261-62;  "Science  Takes 
Doctors'  Lives:  Voluntarily  They  Assume  Risks  in  Studying  Various  Forms  of 
Disease,"  Boston  Herald,  17  July  1910,  clipping  in  "1909-1911  Scrapbook," 
box  3,  U.S.  Public  Health  Service  Scrapbooks,  Manuscripts  Collection,  NLM; 
PH-MHS,  Annual  Report,  1905,  216—17.  Some  of  the  hookworm  control 
methods  developed  by  King,  Ashford,  and  Gutierrez  were  later  adapted  by 
the  Rockefeller  Hookworm  Commission  for  use  in  the  southern  United  States. 

13.  There  are  virtually  no  primary  records  available  regarding  King's  work 
on  spotted  fever.  His  comments  on  Ricketts  were  made  to  a  newspaper  reporter 
shortly  after  Ricketts  died  of  typhus.  See  "Science  Takes  Doctors'  Lives,"  cited 
above. 

14.  My  discussion  of  these  methods  follows  Paul  Clark's  summary  in  Pioneer 
Microbiologists,  96—98. 

15.  Ricketts  to  Tuttle,  29  June  1906,  box  8,  folder  9,  Ricketts  Papers;  MSBH, 
Third  Biennial  Report,  23-24,  26;  Howard  Taylor  Ricketts,  "The  Study  of 
'Rocky  Mountain  Spotted  Fever'  (Tick  Fever?)  by  Means  of  Animal  Inocu- 
lations," JAMA  47  (i9o6):33.  Rabbits  were  later  proven  to  be  susceptible  to 
spotted  fever,  but  they  never  displayed  so  marked  a  reaction  as  did  guinea 
pigs.  See  Liborio  Gomez,  "Rocky  Mountain  Spotted  Fever  in  the  Rabbit," 
/.  Inf.  Dis.  6  (i909):383-86. 

16.  Daily  Missoulian,  15  and  24  May  1906,  as  cited  in  Philip,  "JournaHstic 
View,"  153;  MSBH,  Third  Biennial  Report,  34. 

17.  MSBH,  Third  Biennial  Report,  24-28;  Ricketts  to  Tuttle,  29  June  1906, 
box  8,  folder  9,  Ricketts  Papers;  Ricketts,  "Study  of  'Rocky  Mountain  Spotted 
Fever'  (Tick  Fever?)  by  means  of  Animal  Inoculations,"  33—36, 

18.  A  newspaper  account  stated  that  "it  is  feared"  Etta  Bradley  "cannot 
recover."  She  did  recover,  however,  and  lived  in  the  Bitterroot  until  her  death 
in  1980.  See  Daily  Missoulian,  13  June  1906,  as  cited  in  Philip,  "Journalistic 


Notes  to  Pages  55-57 


^77 


View,"  155;  William  L.  Jellison,  "Jellison  Recalls  Bradley  Contribution,"  Ra- 
valli Republic^  19  November  1980,  9.  Robert  N.  Philip,  in  a  personal  com- 
munication to  the  author,  i6  February  1988,  noted  that  in  1962,  fifty-six 
years  after  her  illness,  Etta  Bradley  McKinney's  blood  still  produced  a  com- 
plement fixation  titer  of  1:8. 

19.  Ricketts  to  Tuttle,  29  June  1906,  box  8,  folder  9,  Ricketts  Papers;  MSBH, 
Third  Biennial  Report,  is-z6;  Ricketts,  "Study  of  'Rocky  Mountain  Spotted 
Fever'  (Tick  Fever?)  by  Means  of  Animal  Inoculations,"  34. 

20.  R.  R.  Parker,  "Certain  Phases  of  the  Problem  of  Rocky  Mountain  Spotted 
Fever:  A  Summary  of  Present  Information,"  Archives  of  Pathology  15 
(i933):398-429  (first  demonstration  of  tick  transmission  of  human  disease 
in  United  States  noted  on  p.  400) ;  Walter  W.  King,  "Experimental  Transmission 
of  Rocky  Mountain  Spotted  Fever  by  Means  of  the  Tick,"  Pub.  Health  Rep. 
21  (1906)  1863-64;  Ricketts,  "The  Transmission  of  Rocky  Mountain  Spotted 
Fever  by  the  Bite  of  the  Wood  Tick  {Dermacentor  occidentalis),''  JAMA  47 
(i906):358. 

21.  Ricketts,  "Transmission  of  Rocky  Mountain  Spotted  Fever,"  358.  The 
question  of  scientific  priority  has  alv^ays  been  a  sensitive  issue.  Rolla  E.  Dyer, 
himself  a  distinguished  rickettsial  investigator  and  director  of  the  NIH,  inserted 
a  handwritten  note  on  King's  article  — in  the  copy  now  held  in  the  NIH  Hbrary — 
to  reemphasize  King's  priority  to  later  readers.  Dated  12  May  193 1,  it  reads: 
"W.  W.  King  returned  to  Hy.  Lab.  from  Montana  June  29,  1906.  Ricketts  fed 
his  first  ticks  on  an  infected  pig  June  19,  1906.  Placed  them  on  non-infected 
pig  on  June  23,  1906.  This  pig  developed  fever  June  27,  1906.  Therefore  the 
experiments  of  King  and  Ricketts  must  have  run  concurrently.  King  certainly 
started  his  experiment  before  Ricketts's  experiment  was  positive.  King's  pub- 
lication precedes  Ricketts.  Therefore,  the  priority  belongs  to  King— although 
Ricketts  may  have  first  suggested  the  experiment." 

22.  Ricketts  to  Tuttle,  25  June  1906,  box  8,  folder  9,  Ricketts  Papers. 

23.  For  example,  in  1908,  Ricketts  refused  the  request  of  a  Dr.  Smith  for 
ticks  infected  with  spotted  fever.  "It  doesn't  sound  generous,"  he  wrote,  but 
explained  that  he  had  reached  this  position  "as  a  result  of  some  unpleasant 
experiences  which  I  want  to  avoid  in  the  future."  See  Ricketts  to  Maria  B. 
Maver,  18  June  1908,  box  8,  folder  11,  Ricketts  Papers.  Walter  W.  King  also 
noted  that  Ricketts  was  "a  little  given  to  reticence  about  results  he  had  obtained 
until  ready  to  make  them  pubhc."  See  "Science  Takes  Doctors'  Lives." 

24.  "The  Transmission  of  Rocky  Mountain  Spotted  Fever  by  Ticks,"  JAMA 
47  (i9o6):366. 

25.  MSBH,  Third  Biennial  Report,  34-35;  "State  Association  Meeting," 
JAMA  46  (1906):  1704. 

26.  "The  Value  of  the  People  of  Montana,"  in  MSBH,  Third  Biennial  Report, 
12-20  (quotations  from  pp.  18-20);  "Investigation  of  the  Cause  and  Means 
of  Prevention  of  Rocky  Mountain  Spotted  Fever  Carried  on  During  1907  and 
1908  by  Dr.  Howard  Taylor  Ricketts  of  the  University  of  Chicago,"  in  MSBH, 
Fourth  Biennial  Report,  78. 

27.  Ricketts  to  Tuttle,  29  June  1906,  box  8,  folder  9,  Ricketts  Papers;  MSBH, 
Third  Biennial  Report,  29. 

28.  See  newspaper  requests  for  citizens  to  collect  ticks  for  both  King  and 
Ricketts  in  Western  News,  29  November  and  19  December  1906,  and  Stev- 
ensville  Register,  8  August  and  26  December  1906,  as  cited  in  Philip,  "Jour- 
nahstic  View,"  153-54. 


278 


Notes  to  Pages  S7~59 


29.  T.  W.  Goodspeed  to  Ricketts,  21  March  1907,  box  4,  folder  15,  Ricketts 
Papers.  Goodspeed  was  secretary  of  the  University  of  Chicago  Board  of  Trus- 
tees. In  a  personal  communication  to  the  author,  16  February  1988,  Robert 
N.  Philip  commented  on  the  four  nymphal  ticks  "taken  from  horses"  that 
Ricketts  used  for  his  early  experiments:  "Very  likely  these  were  D.  albipictus 
(the  elk  winter  tick),  which  at  that  time  had  not  yet  been  distinguished  from 
'D.  occidentalis'  [actually  D.  andersoni].  D.  albipictus  is  a  one-host  tick,  active 
in  the  winter  time.  D.  andersoni  nymphs  are  seldom  active  in  the  winter,  and 
seldom  found  on  large  animals.  Because  it  is  strictly  a  one-host  tick,  D.  al- 
bipictus was  never  considered  to  be  important  in  the  transmission  cycle  and 
hence,  to  my  knowledge,  was  never  tested  for  its  experimental  transmission 
potential  by  Ralph  R.  Parker.  My  father  [Cornelius  B.  Philip]  raised  this 
question  some  years  ago."  See  C.  B.  Philip  and  G.  M.  Kohls,  "Elk,  Winter 
Ticks,  and  Rocky  Mountain  Spotted  Fever:  A  Query,"  Pub.  Health  Rep.  66 
(i952):i672-75. 

30.  Ricketts  to  Hektoen,  4  June  1907,  box  8,  folder  10,  Ricketts  papers; 
Howard  Taylor  Ricketts,  "Observations  on  the  Virus  and  Means  of  Trans- 
mission of  Rocky  Mountain  Spotted  Fever,"  /.  Inf.  Dis.  4  (1907):  141-53. 

31.  Ricketts  to  Tuttle,  19  April  1907,  box  8,  folder  10,  Ricketts  Papers; 
Turtle  to  Ricketts,  3  May  1907,  in  Howard  Taylor  Ricketts,  Scrapbook,  39, 
prepared  by  his  family  and  deposited  in  selected  libraries.  The  NLM  has  a 
copy.  Holden's  death  on  22  April  was  reported  in  the  Western  News.,  23  April 
1907,  as  cited  in  Philip,  "Journalistic  View,"  161. 

32.  William  M.  Chowning,  "Studies  in  Rocky  Mountain  Spotted  Fever," 
/.  Minn.  Med.  Assn.  6c  Northwest  Lancet  28  (i9o8):45-49.  Chowning  in- 
cluded eighteen  microphotographs  from  case  studies  in  this  paper,  but  because 
of  the  diversity  of  the  organisms,  he  did  not  claim  that  any  particular  one 
caused  spotted  fever. 

33.  Ricketts  to  [Hektoen],  n.d.,  box  8,  folder  10,  Ricketts  Papers.  The  first 
page  of  this  letter  is  missing,  but  from  the  context  it  is  clearly  addressed  to 
Hektoen. 

34.  Ricketts  to  Hektoen,  4  June  1907,  box  8,  folder  10,  Ricketts  Papers. 

35.  King's  detachment  from  the  Hygienic  Laboratory  and  detail  to  San 
Francisco  are  noted  in  the  Hygienic  Laboratory  Register,  30  July  and  22  August 
1907,  U.S.  Hygienic  Laboratory  Registers,  1901—23,  Manuscripts  Collection, 
NLM  (hereafter  cited  as  Hygienic  Laboratory  Registers,  NLM);  his  later  po- 
sitions are  noted  in  "Science  Takes  Doctors'  Lives";  PH-MHS,  Annual  Report, 
1911,  272. 

36.  Howard  Taylor  Ricketts,  "A  Micro-Organism  Which  Apparently  Has 
a  Specific  Relationship  to  Rocky  Mountain  Spotted  Fever:  A  Preliminary  Re- 
port," JAMA  52  (1909): 3 79— 80.  Ricketts  also  discussed  these  findings  in  the 
Wesley  M.  Carpenter  Lecture  at  the  New  York  Academy  of  Medicine.  See 
idem,  "Some  Aspects  of  Rocky  Mountain  Spotted  Fever  as  Shown  by  Recent 
Investigations,"  in  idem,  Contributions  to  Medical  Science,  373-408. 

37.  Howard  Taylor  Ricketts,  "Spotted  Fever  Report  No.  i:  General  Report 
of  an  Investigation  of  Rocky  Mountain  Spotted  Fever,  Carried  on  during  1906 
and  1907,"  in  MSBH,  Fourth  Biennial  Report,  109;  idem,  "A  Summary  of 
Investigations  of  the  Nature  and  Means  of  Transmission  of  Rocky  Mountain 
Spotted  Fever,"  Transactions  of  the  Chicago  Pathological  Society  7  ( 1907):  73- 
82. 


Notes  to  Pages 

I 


279 


38.  Ricketts  to  Turtle,  24  June  1909,  folder  i,  "Rocky  Mounrain  Sporred 
Fever,  1908-1911,"  box  i,  "General  Correspondence,"  MSBH  Records.  See 
also  Ricketts,  "The  Role  of  the  Wood-tick  {Dermacentor  occidentalis)  in  Rocky 
Mountain  Spotted  Fever,  and  the  Susceptibility  of  Local  Animals  to  This 
Disease:  A  Preliminary  Report,"  ]AMA  49  [t^oj):z^—zj\  idem,  "Further 
Experiments  with  the  Wood-Tick  in  Relation  to  Rocky  Mountain  Spotted 
Fever," /AMA  49  (1907):  1278-81. 

39.  Maria  B.  Maver,  "Transmission  of  Spotted  Fever  by  Other  Than  Mon- 
tana and  Idaho  Ticks,"  /.  Inf.  Dis.  8  (191 1)1322-26;  idem,  "Transmission  of 
Spotted  Fever  by  the  Tick  in  Nature,"  ibid.,  327-29.  See  also  correspondence 
about  these  experiments  in  box  8,  folder  12,  Ricketts  Papers.  The  common 
dog  tick  is  known  as  Dermacentor  variabilis  (Say),  the  "lone  star"  tick  as 
Amblyomma  americanum  (Linnaeus),  and  the  Utah  rabbit  tick  as  Dermacentor 
parumapertus. 

40.  Ricketts,  "Spotted  Fever  Report  No.  i,"  99-100. 

41.  Ibid.,  100-105. 

42.  Ibid.,  120;  Ricketts  to  Tuttle,  23  November  1908,  folder  i,  "Rocky 
Mountain  Spotted  Fever,  1908-19 11,"  box  i,  "General  Correspondence," 
MSBH  Records. 

43.  Ricketts,  "Spotted  Fever  Report  No.  i,"  121-24. 

44.  Ricketts  to  Tuttle,  8  January  1908;  and  Morgan  to  Ricketts,  n.d.  but 
late  January  1908,  from  context,  folder  i,  "Rocky  Mountain  Spotted  Fever, 
1908-19 1 1,"  box  I,  "General  Correspondence,"  MSBH  Records;  Ricketts, 
"Spotted  Fever  Report  No.  i,"  124. 

45.  Ricketts,  "Spotted  Fever  Report  No.  i,"  129-30;  Ricketts  to  Tuttle,  19 
January  1908,  folder  i,  "Rocky  Mountain  Spotted  Fever,  1908— 191 1,"  box 
I,  "General  Correspondence,"  MSBH  Records.  Montana  State  College  is  now 
called  Montana  State  University. 

46.  Ricketts  to  Tuttle,  14  January  1908,  folder  i,  "Rocky  Mountain  Spotted 
Fever,  1908-1911,"  box  i,  "General  Correspondence,"  MSBH  Records, 

47.  Ricketts,  "Spotted  Fever  Report  No.  i,"  126. 

48.  Ibid.,  126-27. 

49.  Quotation  from  ibid.,  127;  Josiah  J.  Moore,  "Time  Relationships  of 
the  Wood-Tick  in  the  Transmission  of  Rocky  Mountain  Spotted  Fever,"  /.  Inf. 
Dis.  8  (i9ii):339-47. 

50.  Western  News,  19  June  1907,  as  cited  in  Philip,  "Journalistic  View," 
161;  "Investors  Flock  to  the  Bitter  Root  Valley:  Exhibition  Takes  Chicago  by 
Storm!"  Western  News,  13  November  1907,  and,  on  cherries.  Western  News, 
5  August  1908,  both  cited  in  Philip,  "Journalistic  View,"  157,  164;  Tuttle  to 
Ricketts,  23  October  1909;  and  Ricketts  to  Tuttle,  9  November  1909,  folder 
I,  "Rocky  Mountain  Spotted  Fever,  1908-1911,"  box  i,  "General  Corre- 
spondence," MSBH  Records. 

51.  Ricketts  to  Hektoen,  4  June  1907,  box  8,  folder  10,  Ricketts  Papers. 
For  a  more  complete  discussion  of  these  techniques,  see  George  Clark  and 
Frederick  H.  Kasten,  History  of  Staining,  3d  ed.  (Baltimore:  Williams  & 
Wilkins,  1983),  esp.  1 13-17.  For  a  complete  statement  of  Koch's  postulates, 
see  chap.  3,  n.  22. 

52.  W.  A.  Hooker,  "A  Review  of  the  Present  Knowledge  of  the  Role  of 
Ticks  in  the  Transmission  of  Disease,"  Journal  of  Economic  Entomology  1 
(i9o8):65-76,  esp.  charts  on  pp.  68,  69,  74;  Rennie  W.  Doane,  Insects  and 


zSo 


Notes  to  Pages  64-68 


Disease:  A  Popular  Account  of  the  Way  in  Which  Insects  May  Spread  or  Cause 
Some  of  Our  Common  Diseases  (New  York:  Henry  Holt,  1910),  32. 

5  3 .  Ricketts,  "A  Micro-Organism,"  3  79,  3  80.  In  this  original  article,  Ricketts 
gave  the  dilutions  as  "up  to  i  to  160."  This  was  in  error;  the  actual  dilutions 
were  up  to  i  to  3  20.  See  Ricketts,  letter  of  correction  to  the  editor,  JAMA  5  2 
(1909):  491. 

54.  Ricketts,  "Some  Aspects  of  Rocky  Mountain  Spotted  Fever  as  Shown 
by  Recent  Investigations,"  397-98. 

55.  Idem,  "A  Micro-Organism,"  380. 

56.  Ricketts  to  Tuttle,  25  January  1909,  folder  i,  "Rocky  Mountain  Spotted 
Fever,  1908-19 11,"  box  i,  "General  Correspondence,"  MSBH  Records;  Novy 
to  Ricketts,  6  April  1909;  and  Chowning  to  Ricketts,  13  July  1909,  box  8, 
folder  12,  Ricketts  Papers. 

57.  Ricketts  to  Tuttle,  17  March  1909;  and  Ricketts  to  Tuttle,  24  June 
1909,  folder  I,  "Rocky  Mountain  Spotted  Fever,  1908-1911,"  box  i,  "General 
Correspondence,"  MSBH  Records;  McCampbell  to  Ricketts,  22  November 
1909,  box  8,  folder  12,  Ricketts  Papers. 

58.  Ricketts  to  Hektoen,  4  June  1907,  box  8,  folder  10,  Ricketts  Papers; 
Howard  Taylor  Ricketts  and  Liborio  Gomez,  "Studies  on  Immunity  in  Rocky 
Mountain  Spotted  Fever:  First  Communication,"  /.  Inf.  Dis.  5  (i9o8):22i- 
44  (quotations  from  p.  235). 

59.  Ricketts  and  Gomez,  "Studies  on  Immunity,"  224,  236. 

60.  Ibid.,  228—30,  236—42. 

61.  Ricketts  to  Tuttle,  17  March  1909;  and  Ricketts  to  Tuttle,  24  June 
1909,  folder  I,  "Rocky  Mountain  Spotted  Fever,  1908-1911,"  box  i,  "General 
Correspondence,"  MSBH  Records. 

62.  McCampbell  to  Ricketts,  8  August  1909;  Ricketts  to  Hektoen,  23 
December  1909;  and  Ricketts  to  S.  A.  Matthews,  8  October  1909,  box  8, 
folder  12,  Ricketts  Papers. 

63.  Ricketts  to  Hektoen,  4  June  1907,  box  8,  folder  10,  Ricketts  Papers. 

64.  Ricketts  and  Gomez,  "Studies  on  Immunity,"  230—32;  Howard  Taylor 
Ricketts,  "Spotted  Fever  Report  No.  2:  A  Report  of  Investigations  Carried  on 
during  the  Winter  of  1907—8  and  the  Spring  and  Summer  of  1908,"  in  MSBH, 
Fourth  Biennial  Report,  138-42;  Ricketts  to  Tuttle,  21  March  1908,  folder 
I,  "Rocky  Mountain  Spotted  Fever,  1908-19 11,"  box  i,  "General  Corre- 
spondence," MSBH  Records. 

65.  These  cases  are  discussed  in  Ricketts,  "Spotted  Fever  Report  No.  2," 
144—49  (quotation  from  p.  146). 

66.  All  three  recovered  cases  are  identifiable  in  local  press  accounts.  One 
paper  attributed  to  the  serum  the  recovery  of  a  case  that  Ricketts  himself  never 
recorded.  For  all  these  cases  see  Philip,  "Journalistic  View,"  167—68. 

67.  Ricketts  to  Tuttle,  29  March  1909;  and  Ricketts  to  Tuttle,  24  June 
1909,  folder  I,  "Rocky  Mountain  Spotted  Fever,  1908-191 1,"  box  i,  "General 
Correspondence,"  MSBH  Records.  The  serum  sent  in  1909  reportedly  saved 
the  life  of  Mrs.  Harry  H.  Townsend,  whose  grateful  husband  wrote  a  letter 
of  appreciation  to  their  perceived  benefactor.  See  Stevensville  Register.,  17  June 
1909,  as  cited  in  Philip,  "Journalistic  View,"  176;  Harry  H.  Townsend  to 
Ricketts,  31  March  1910,  box  8,  folder  13,  Ricketts  Papers. 

68.  Tuttle  to  Ricketts,  25  February  1908,  folder  i,  "Rocky  Mountain  Spotted 
Fever,  1908-1911,"  box  i,  "General  Correspondence,"  MSBH  Records; 


Notes  to  Pages  68-yi  281 

MSBH  Minutes,  special  session,  19  February  1908;  Ricketts  to  Tuttle,  22 
October  1908;  and  [Ricketts  and  Tuttle],  unsigned  letter,  to  E.  E.  Maxey,  24 
October  1908,  folder  i,  "Rocky  Mountain  Spotted  Fever,  1908-1911,"  box 
I,  "General  Correspondence,"  MSBH  Records. 

69.  Tuttle  to  Ricketts,  5  March  1909;  and  Ricketts  to  Tuttle,  17  March 
1909,  folder  I,  "Rocky  Mountain  Spotted  Fever,  1908-1911,"  box  i,  "General 
Correspondence,"  MSBH  Records.  The  bill  passed  the  legislature  on  4  March. 

70.  MSBH  Minutes,  i  April  1909;  Tuttle  to  Cooley,  22  March  1909,  folder 
I,  "Rocky  Mountain  Spotted  Fever,  1908-1911,"  box  1,  "General  Corre- 
spondence," MSBH  Records. 

71.  Romney  to  Tuttle,  25  April  1909;  President,  Montana  Medical  Asso- 
ciation, to  Board  of  Education,  4  June  1909;  and  Ricketts  to  Tuttle,  24  June 
1909,  folder  I,  "Rocky  Mountain  Spotted  Fever,  1908-1911,"  box  i,  "General 
Correspondence,"  MSBH  Records;  Daily  Missoulian,  14  May  1909,  as  cited 
in  Philip,  "JournaHstic  Vievs^,"  176. 

72.  MSBH  Minutes,  i  April  1909.  See  also  correspondence  in  box  8,  folder 
12,  Ricketts  Papers,  regarding  Ricketts's  attempt  to  discuss  this  with  the  state 
board  of  examiners  when  the  members  of  that  body  went  to  Chicago  in  late 
April  1909. 

73.  See  correspondence  in  box  4,  folder  15,  Ricketts  Papers,  about  Ricketts's 
offers  of  positions.  Ricketts  received  the  gold  medal  for  an  exhibit  on  spotted 
fever  research  prepared  by  his  assistant  Maria  B.  Maver.  See  Ricketts  to  Maver, 
18  June  1908,  box  8,  folder  11,  Ricketts  Papers. 

74.  Preliminary  negotiations  and  financial  arrangements  for  the  typhus  in- 
vestigations are  documented  in  box  8,  folder  12,  and  box  4,  folder  15,  Ricketts 
Papers;  quotation  from  Ricketts  to  H.  G.  Wells,  12  February  19 10,  box  8, 
folder  13,  Ricketts  Papers.  On  Ricketts's  decision  to  go  to  Mexico,  see  also 
Russell  M.  Wilder,  "The  Rickettsial  Diseases:  Discovery  and  Conquest,"  Arch. 
Pathol.  49  (i95o):479-89. 

75.  Charles  Nicolle,  C.  Comte,  and  E.  Conseil,  "Transmission  experimentale 
du  typhus  exanthematique  par  le  pou  du  corps,"  Comptes  Rendus  de  V Aca- 
demic des  Sciences  149  (i909):486-89  (hereafter  cited  as  Compt.  Rend.  Acad, 
d.  Sc.);  Wilder,  "Rickettsial  Diseases,"  483-84;  John  F.  Anderson  and  Joseph 
Goldberger,  "On  the  Relation  of  Rocky  Mountain  Spotted  Fever  to  the  Typhus 
Fever  of  Mexico:  A  Preliminary  Note,"  Pub.  Health  Rep.  24  (i909):i86i- 
62;  Goldberger  to  Ricketts,  8  March  19 10,  Ricketts,  Scrapbook,  109;  Howard 
Taylor  Ricketts  and  Russell  M.  Wilder,  "The  Etiology  of  the  Typhus  Fever 
(Tabardillo)  of  Mexico  City:  A  Further  Preliminary  Report,"  JAMA  54 
(1910):  1373-75.  The  entire  series  of  Ricketts's  and  Wilder's  papers  on  typhus 
are  in  Ricketts,  Contributions  to  Medical  Science,  451-500. 

76.  Ricketts  to  Tuttle,  13  February  19 10;  Ricketts  to  Tuttle,  12  March  19 10; 
Tuttle  to  Ricketts,  18  March  19 10;  and  Ricketts  to  Moore,  14  April  19 10, 
box  8,  folder  13,  Ricketts  Papers. 

77.  Ricketts  to  Moore,  14  April  1910;  Moore  to  Ricketts,  13  April  1910; 
and  Ricketts  to  H.  G.  Wells,  12  February  19 10,  box  8,  folder  13,  Ricketts 
Papers. 

78.  Wilder  to  Tuttle,  25  April  1910,  folder  i,  "Rocky  Mountain  Spotted 
Fever,  1908-1911,"  box  i,  "General  Correspondence,"  MSBH  Records.  See 
references  to  Ricketts's  illness  in  box  8,  folder  12,  Ricketts  Papers.  Daily 
Missoulian,  5  May  19 10,  as  cited  in  Philip,  "Journalistic  View,"  179. 


282 


Notes  to  Pages  71-7S 


79.  Turtle  to  Moore,  telegram,  4  May  19 10;  and  Wilder  to  Tuttle,  25  April 
1910,  folder  I,  "Rocky  Mountain  Spotted  Fever,  1908-1911,"  box  i,  "General 
Correspondence,"  MSBH  Records;  Ricketts  to  Judson,  23  April  1909,  box  4, 
folder  15,  Ricketts  Papers. 

80.  R  G.  Heinemann  and  Josiah  J.  Moore,  for  example,  attempted  to  develop 
a  more  concentrated  form  of  Ricketts's  antiserum.  The  few  human  trials  of 
its  efficacy,  however,  were  inconclusive.  See  Heinemann  and  Moore,  "The 
Production  and  Concentration  of  a  Serum  for  Rocky  Mountain  Spotted  Fever: 
Preliminary  Note,"  JAMA  57  (191 1):  198;  idem,  "Experimental  Therapy  of 
Rocky  Mountain  Spotted  Fever:  The  Preventive  and  Curative  Action  of  a 
Serum  for  Spotted  Fever,  and  the  Inefficiency  of  Sodium  Cacodylate  as  a 
Curative  Agent  for  This  Disease  in  Guinea  Pigs,"  /.  Inf.  Dis.  10  ( 19 12):  294- 
304.  Other  work  by  Ricketts's  students  and  colleagues,  published  in  Ricketts, 
Contributions  to  Medical  Science,  will  be  discussed  and  cited  in  later  chapters. 

81.  See  correspondence  regarding  this  in  box  8,  folder  13,  Ricketts  Papers. 

Chapter  Five:  Tick  Eradication  Efforts,  ipii-i^zo 

1.  Cornelius  B.  Philip  and  Lloyd  E.  Rozeboom,  "Medico-Veterinary  En- 
tomology: A  Generation  of  Progress,"  in  Ray  F.  Smith,  Thomas  E.  Mittler, 
and  Carroll  N.  Smith,  eds..  History  of  Entomology  (Palo  Alto,  Calif.:  Annual 
Reviews,  1973),  333;  R.  Hoeppli,  Parasites  and  Parasitic  Infections  in  Early 
Medicine  and  Science  (Singapore:  University  of  Malaya  Press,  1959),  187- 
88. 

2.  Taxonomic  systematics  are  discussed  in  most  textbooks  of  zoology.  My 
discussion  follows  that  in  William  B.  Herms,  Medical  Entomology:  With 
Special  Reference  to  the  Health  and  Well-Being  of  Man  and  Animals  (New 
York:  Macmillan,  1939),  29-31, 422-23;  and  Wolbach's  review  of  the  spotted 
fever  tick  in  his  "Studies  on  Rocky  Mountain  Spotted  Fever"  (see  chap.  4,  n. 
7),  46-48.  The  word  Dermacentor  is  derived  from  the  Greek  dermis.,  "skin," 
and  kentor,  "stinger,"  "pricker,"  or  "goader." 

3.  Report  of  Louis  B.  Wilson  and  William  M.  Chowning  in  MSBH,  First 
Biennial  Report,  27. 

4.  Wilson  and  Chowning,  "Studies  in  Pyroplasmosis  Hominis"  (see  chap. 
3,  n.  9),  51-52. 

5.  Stiles,  "Zoological  Investigation"  (see  chap.  3,  n.  4),  7;  King,  "Experi- 
mental Transmission"  (see  chap.  4,  n.  20),  863;  Ricketts,  "Role  of  the  Wood- 
Tick"  (see  chap.  4,  n.  38),  24. 

6.  Nathan  Banks,  "A  Revision  of  the  Ixodoidea,  or  Ticks,  of  the  United 
States,"  Technical  Services,  Bureau  of  Entomology,  U.S.  Department  of  Ag- 
riculture Bulletin  no.  15  (1908).  The  species  name  venustus  means  "lovely," 
"charming,"  or  "beautiful." 

7.  Charles  Wardell  Stiles,  "The  Common  Tick  {Dermacentor  andersoni)  of 
the  Bitter  Root  Valley,"  Pub.  Health  Rep.  23  (i9o8):949;  idem,  "The  Tax- 
onomic Value  of  the  Microscopic  Structure  of  the  Stigmal  Plates  in  the  Tick 
Genus  Dermacentor,"  U.S.  Hygienic  Laboratory  Bulletin  no.  62  (August  19 10), 
72  pp.  and  43  plates;  idem,  "The  Correct  Name  of  the  Rocky  Mountain 
Spotted  Fever  Tick,"  ]AMA  55  (19 10):  1909-10;  Nathan  Banks,  letter  to  the 
editor,  JAMA  55  (1910):  1574-75. 

8.  See,  for  example,  MSBE,  First  Biennial  Report,  12,  28. 


Notes  to  Pages  75-77 


283 


9.  "Opinion  78 :  Case  of  Dermacentor  andersoni  vs.  Dermacentor  venustus," 
in  "Opinions  Rendered  by  the  International  Commission  on  Zoological  No- 
menclature: Opinions  78  to  81,"  Smithsonian  Miscellaneous  Collections  73, 
no.  2  (i924):i-i4  (quotation  from  pp.  13-14).  The  effect  of  this  ruling, 
however,  made  D.  venustus  a  vaHd  "senior  synonym"  for  D.  andersoni  if  the 
names  were  applied  to  a  single  species.  In  1976  an  RML  entomologist,  James 
E.  Keirans,  with  the  support  of  many  of  his  colleagues,  successfully  applied 
to  the  International  Commission  on  Zoological  Nomenclature  to  have  the 
name  D.  venustus  suppressed  entirely,  so  that  the  name  D.  andersoni  alone 
is  now  the  official  name  for  the  Rocky  Mountain  wood  tick.  See  James  E. 
Keirans,  "Dermacentor  venustus  Marx  MS.  in  Neumann,  1897:  Proposed 
Suppression  under  the  Plenary  Powers  so  as  to  Conserve  Dermacentor  an- 
dersoni Stiles,  1908  (Acarina:  Ixodidae).  Z.N.(S.)  260,"  Bulletin  of  Zoological 
Nomenclature  32  (i976):26i-64.  I  am  grateful  to  Dr.  Keirans  for  providing 
me  with  a  copy  of  this  paper. 

10.  As  late  as  1928,  for  example,  L.  O.  Howard,  chief  of  the  U.S.  Bureau 
of  Entomology,  told  delegates  to  an  international  congress  of  entomologists 
that  zoologists,  because  of  their  conservatism,  had  consistently  "slighted" 
entomology.  See  "Age  of  Insects,  Not  Man,  Says  Dr.  L.  O.  Howard  Opening 
Entomology  Congress  Here,'"  Journal-News  (Ithaca,  N.Y.),  13  August  1928, 
clipping  in  RML  Scrapbook  "1919-1931." 

11.  On  early  entomological  research  see  Gustavus  A.  Weber,  The  Bureau 
of  Entomology:  Its  History,  Activities,  and  Organization,  Institute  for  Gov- 
ernment Research,  Service  Monographs  of  the  United  States  Government  no. 
60  (Washington,  D.C.:  Brookings  Institution,  1930),  1-13.  On  insect  threats 
in  1876  see  James  Harvey  Young,  "Harper's  Weekly  on  Health  in  America, 
1876,"/.  Hist.  Med.  Allied  Sci.  41  (i986):i56-74,  esp.  162. 

12.  Robert  H.  Wiebe,  The  Search  for  Order,  1877-1910  (New  York:  Hill 
&  Wang,  1967);  William  B.  Herms,  "Medical  Entomology,  Its  Scope  and 
Methods,"/.  Econ.  Entomol.  2  (i909):265-68. 

13.  It  has  been  argued,  for  example,  that  veterinarian  Fred  L.  Kilbourne 
was  slighted  in  the  allocation  of  credit  for  the  Texas  cattle  fever  tick  trans- 
mission experiments  because  his  physician-supervisor,  Theobald  Smith, 
claimed  first-author  privilege  on  their  classic  report.  See  J.  F.  Smithcors,  "Dis- 
covery of  the  Arthropod  Vector  of  Disease,"  Modern  Veterinary  Practice  62 
(i98i):37i-74. 

14.  Turtle  to  Wyman,  2  March  191 1;  and  Thomas  B.  McClintic,  "Mem- 
orandum Relative  to  Investigations  of  Rocky  Mountain  Spotted  Fever,"  5  July 
1911,  file  1266,  box  119,  Central  File,  1897-1923,  PHS  Records;  PH-MHS, 
Annual  Report,  191 1,  40—42. 

15.  Biographical  information  on  McClintic  is  taken  from  his  personnel  file, 
Record  Group  090-78,  Accession  no.  0001,  Agency  Box  no.  OF,  Records 
Center  Location  no.  FU#  134867  through  FU#  134992,  box  #  77,  NARA, 
Saint  Louis  (hereafter  cited  as  McClintic  personnel  file,  NARA,  Saint  Louis); 
Blue  to  F.  M.  Wilmot,  25  November  19 12,  in  ibid.;  McClintic,  "Memorandum 
Relative  to  Investigations." 

16.  McClintic  to  Wyman,  5  July  191 1,  file  1266,  box  119,  Central  File, 
1 897-1923,  PHS  Records. 

17.  McClintic  to  Wyman,  7  July  1911,  file  1266,  box  119,  Central  File, 
1 897-1923,  PHS  Records. 


284 


Notes  to  Pages  77-81 


18.  For  biographical  information  on  Cooley  see  his  curriculum  vitae,  file 
"Zoology  and  Entomology  Bibliography,"  Archives  Department,  Renne  Li- 
brary, Montana  State  University,  Bozeman;  obituary  by  Glen  M.  Kohls, 
/.  Econ.  Entomol.  62.  {i^6^):^j2..  For  a  history  of  the  development  of  entomol- 
ogy as  a  graduate  program  at  Massachusetts  Agricultural  College,  see  Entomol- 
ogy and  Zoology  at  the  Massachusetts  Agricultural  College  (Amherst,  Mass.: 
Massachusetts  Agricultural  College,  191 1)  (esp.  Warren  E.  Hinds's  article  by 
the  same  title),  15-2.7.  This  institution  later  became  the  University  of  Mas- 
sachusetts. 

19.  Robert  A.  Cooley,  "Notes  on  Spotted  Fever,"  manuscript,  1953,  in  RML 
Scrapbook  "1942—  ";  idem,  "Preliminary  Report  on  the  Wood  Tick,  Der- 
macentor  sp.,''  Montana  Agricultural  Experiment  Station  Bulletin  no.  75 
(i909):95-i04.  Ricketts  to  Tuttle,  9  November  1908,  folder  i,  "Rocky  Moun- 
tain Spotted  Fever,  1908-1911,"  box  i,  "General  Correspondence,"  MSBH 
Records;  Cooley  to  Tuttle,  16  November  1908,  vol.  "W.  F.  Cogswell,  A.  H. 
McCray,  T.  D.  Tuttle,"  CC. 

20.  The  results  of  the  tick  survey  w^ere  published  in  F.  C.  Bishopp,  "The 
Distribution  of  the  Rocky  Mountain  Spotted  Fever  Tick,"  U.S.  Bureau  of 
Entomology  Circular  no.  136  (191 1);  W.  D.  Hunter  and  F.  C.  Bishopp,  "The 
Rocky  Mountain  Spotted  Fever  Tick,  with  Special  Reference  to  the  Problem 
of  Its  Control  in  the  Bitter  Root  Valley  in  Montana,"  U.S.  Bureau  of  Ento- 
mology Bulletin  no.  105  (191 1).  On  the  history  of  the  Bureau  of  Biological 
Survey,  see  Jenks  Cameron,  The  Bureau  of  Biological  Survey:  Its  History, 
Activities,  and  Organization,  Institute  for  Government  Research  Service  Mon- 
ographs of  the  United  States  Government  no.  54  (Baltimore:  Johns  Hopkins 
Press,  1929). 

21.  Cooley,  "Notes  on  Spotted  Fever,"  2—3.  Price  relates  the  anecdote  in 
more  detail  in  Fighting  Spotted  Fever  (see  chap.  3,  n.  4),  74-76.  Birdseye 
succeeded  in  publishing  as  first  author  of  one  paper  and  as  junior  author  of 
another,  but  King  did  not.  His  work,  although  acknowledged,  appeared  in 
191 1  under  the  authorship  of  Cooley  and  representatives  of  the  Bureau  of 
Entomology.  See  citations  in  n.  22,  24,  and  27  below.  King  wrote  to  Cooley 
about  Bishopp's  claiming  of  first-author  status  in  King  to  Cooley,  23  December 
19 1 2,  vol.  "W.  V.  King,"  CC. 

22.  Robert  A.  Cooley,  "Tick  Control  in  Relation  to  the  Rocky  Mountain 
Spotted  Fever:  A  Report  of  Cooperative  Investigations  Conducted  by  the 
Bureau  of  Entomology  and  the  Montana  Experiment  Station,"  Montana  Ag- 
ricultural College  Experiment  Station  Bulletin  no.  85  (1911):! 8-19. 

23.  Ibid.,  20.  Although  the  men  noted  that  they  used  a  "woolen"  cloth, 
flannel  was  soon  adopted  to  flag  ticks  because  it  is  much  lighter  and  easier  to 
handle.  Game  Warden  J.  L.  DeHart  reminded  Cooley  in  19 14  about  "the 
wanton  slaughter  of  game  in  19 10  by  Mr.  Birdseye's  party."  See  DeHart  to 
Cooley,  7  August  19 14,  vol.  "Montana  State  Officials,"  CC. 

24.  Cooley,  "Tick  Control,"  20-27;  Cooley  to  W.  E.  McMurry,  17  January 
191 1,  vol.  "Montana  State  Officials,"  CC;  W.  H.  Henshaw  and  Clarence 
Birdseye,  "The  Mammals  of  the  Bitter  Root  Valley,  Montana  and  Their  Re- 
lation to  Spotted  Fever,"  U.S.  Bureau  of  Biological  Survey  Bulletin  no.  82 
(1911). 

25.  See  correspondence  regarding  this  in  vol.  "W.  F.  Cogswell,  A.  H.  McCray, 
T.  D.  Tuttle,"  CC. 


Notes  to  Pages  8i-8j 


285 


26.  Cooleyto  Norris,  13  October  19 10;  and  Cooley  to  McMurry,  17  January 
191 1,  vol.  "Montana  State  Officials";  Cooley  to  H.  T.  Fernald,  4  May  191 1, 
vol.  "Professors  at  Various  Universities";  and  Cooley  to  W.  D.  Hunter,  23 
May  191 1,  vol.  "W.  F.  Cogswell,  A.  H.  McCray,  T.  D.  Tuttle,"  CC  (quotation 
from  Cooley  to  McMurry). 

27.  Cooley,  "Notes  on  Spotted  Fever,"  3;  Clarence  Birdseye,  "Some  Com- 
mon Mammals  of  Western  Montana  in  Relation  to  Agriculture  and  Spotted 
Fever,"  U.S.  Department  of  Agriculture  Farmer's  Bulletin  no.  484  (1912). 

28.  Cooley,  "Notes  on  Spotted  Fever,"  4.  According  to  the  entomologists' 
version  of  this  larger  controversy,  Tuttle  later  made  outrageous  and  false 
charges  about  the  dangerous  conditions  under  which  this  experiment  was 
conducted.  See  Cooley  to  King,  13  May  19 12,  vol.  "W.  V.  King,"  CC;  King 
to  Cooley,  3  May  1912,  file  1266,  box  119,  Central  File,  1897— 1923,  PHS 
Records. 

29.  Cooley,  "Tick  Control,"  27-28;  Thomas  D.  Tuttle,  untitled  statement 
opposing  Cooley's  independent  work,  n.d.,  folder  i,  "Rocky  Mountain  Spotted 
Fever,  1908— 191 1,"  box  i,  "General  Correspondence,"  MSBH  Records. 

30.  MSBH  Minutes,  5  June  191 1. 

31.  Thomas  D.  Tuttle,  untitled  statement  opposing  Cooley's  independent 
work  (see  n.  29  above);  MSBH  Minutes,  24  July  191 1. 

32.  King  to  Cooley,  3  May  19 12;  and  Cooley  to  King,  13  May  191 2,  vol. 
"W.  V.  King,"  CC;  MSBH  Minutes,  6  June  191 1;  Montana  State  Archives. 
Howard  to  Cooley,  29  May  191 1,  vol.  "W.  F.  Cogswell,  A.  H.  McCray, 
T  D.  Tuttle,"  CC. 

33.  Thomas  B.  McCHntic,  "Investigations  of  and  Tick  Eradication  in  Rocky 
Mountain  Spotted  Fever:  A  Report  of  Work  Done  on  Spotted  Fever  in  Co- 
operation with  the  State  Board  of  Health  of  Montana,"  Pub.  Health  Rep.  27 
(i9i2):732-6o. 

34.  Ibid.,  734. 

35.  Ibid.,  735;  H.  W.  Graybill,  "Methods  of  Exterminating  the  Texas  Fever 
Ticks,"  U.S.  Department  of  Agriculture  Farmer's  Bulletin  no.  378  (1909). 
After  the  Florence  vat  was  dynamited  in  191 3,  it  was  replaced  by  a  galvanized 
iron  vat. 

36.  McClintic,  "Investigations  and  Tick  Eradication,"  735-36. 

37.  Ibid.,  736-38. 

38.  Ibid.,  733—34;  Harden,  Inventing  the  NIH  (see  chap.  3,  n.  35),  27-39; 
Manfred  Waserman,  "The  Quest  for  a  National  Health  Department  in  the 
Progressive  Era,"  Bull.  Hist.  Med.  49  (i975):353— 80;  George  Rosen,  "The 
Committee  of  One  Hundred  on  National  Health  and  the  Campaign  for  a 
National  Health  Department,  1906— 19 12,"  American  Journal  of  Public  Health 
62  (i972):26i-63. 

39.  Entry  dated  21  November  191 1,  Hygienic  Laboratory  Registers,  NLM; 
Harden,  Inventing  the  NIH,  38-39;  An  Act  to  Change  the  Name  of  the  Public 
Health  and  Marine  Hospital  Service,  to  Increase  the  Pay  of  Officers  of  Said 
Service,  and  for  Other  Purposes,  14  August  19 12,  37  Stat.  L.  309. 

40.  Various  secondary  sources  contain  conflicting  accounts  of  McClintic's 
marriage  and  death  from  spotted  fever.  My  account  is  based  largely  on  a  letter 
seeking  a  pension  for  McClintic's  widow  and  initialed  by  Service  administrators 
who  knew  McClintic  personally:  Andrew  Mellon  to  Harold  Knutson,  5  Feb- 
ruary 1930,  McClintic  personnel  file,  NARA,  Saint  Louis. 


286 


Notes  to  Pages  86-pi 


41.  McClintic,  "Investigations  and  Tick  Eradication,"  746-47;  L.  D.  Pricks, 
ed.,  "Rocky  Mountain  Spotted  Fever:  Some  Investigations  Made  During  19 12 
by  Passed  Asst.  Surg.  T.  B.  McClintic,"  Pub.  Health  Rep.  29  ( 19 14) :  1008- 
20. 

42.  Pricks,  ed.,  "Rocky  Mountain  Spotted  Pever:  McClintic,"  1012,  1019- 
20;  McClintic,  "Investigations  and  Tick  Eradication,"  744-46.  Experiments 
with  coyotes  and  domestic  cats  gave  inconclusive  results. 

43.  McClintic,  "Investigations  and  Tick  Eradication,"  740-42;  Pricks,  ed., 
"Rocky  Mountain  Spotted  Pever:  McClintic,"  1012-19. 

44.  Pricks,  ed.,  "Rocky  Mountain  Spotted  Pever:  McClintic,"  1009-12. 

45.  Andrew^  Mellon  to  Harold  Knutson,  5  February  1930,  McClintic  per- 
sonnel file,  NARA,  Saint  Louis;  "Specialist  Dies  on  Day  of  Arrival  at  Wash- 
ington," Northwest  Tribune,  16  August  19 12;  "Dr.  McClintic  Dies  after  Long 
Journey,"  Western  News,  16  August  191 2;  "Spotted  Pever,"  Western  News, 
3  September  19 12. 

46.  Por  biographical  information  on  Pricks  see  Williams,  United  States  Public 
Health  Service  (see  chap.  3,  n.  39),  195,  296,  302,  545,  559;  Pricks's  personnel 
file,  Record  Group  090—78,  Accession  no.  0001,  Agency  Box  no.  OP,  Records 
Center  Location  no.  PU#i34867  through  PU#i34992,  box  #  41,  NARA, 
Saint  Louis;  "Takes  Up  Study  of  the  Deadly  Spotted  Fever  Bearing  Tick:  Passed 
Assistant  Surgeon  L.  D.  Pricks  Designated  to  Resume  Work  of  Dr.  McClintic, 
Who  Caught  Malady  While  Investigating  It,  and  Died,"  clipping,  n.d.,  RML 
Scrapbook  "1919-1931." 

47.  Price,  Fighting  Spotted  Fever,  96— ^y,  MSBE,  First  Biennial  Report,  6; 
An  Act  to  Create  the  State  Board  of  Entomology.  To  Define  its  Powers  and 
Duties  and  Appropriate  Money  Therefor,  cited  in  MSBE,  First  Biennial  Report, 
5. 

48.  Tuttle  obituary  in  Montana  Record  Herald  (Helena),  9  July  1942.  During 
World  War  I,  Tuttle  served  as  director  of  medical  administration  at  the  can- 
tonments of  Fort  Lew^is  and  Bremerton,  Washington;  later  he  held  a  post  at 
the  U.S.  Veterans  Hospital  at  Saint  Paul,  Minnesota.  He  died  on  24  June  1942 
at  age  seventy-three  from  heart  disease. 

49.  Tuttle  to  W.  C.  Rucker,  23  September  1913,  file  1266,  box  119,  Central 
File,  1 897-1923,  PHS  Records.  Por  biographical  information  on  Cogsw^ell  see 
John  S.  Anderson,  "A  Strange  Disease  in  a  Beautiful  Land,"  Treasure  State 
Health,  Pall  1976,  13-16;  obituary  in  JAMA  161  (i956):i494. 

50.  MSBH  Minutes,  16  December  19 12;  Price,  Fighting  Spotted  Fever,  96- 
97- 

51.  Price,  Fighting  Spotted  Fever,  98-103;  Hunter  to  Cooley,  31  March 
1913,  folder  2,  "Rocky  Mountain  Spotted  Pever,  1912— 1919,"  box  i,  "General 
Correspondence,"  MSBH  Records. 

52.  W.  V.  King,  "Work  of  Bureau  of  Entomology  against  Spotted  Fever  Tick 
in  Co-operation  with  Board,"  in  MSBE,  First  Biennial  Report,  18;  Pricks  to 
Montana  State  Board  of  Entomology,  14  May  191 5,  vol.  "Montana  State 
Officials,"  CC;  "Start  War  on  Wood  Tick,"  Northwest  Tribune,  18  April 
1913. 

53.  Robert  A.  Cooley,  "Communication  from  the  State  Entomologist  to  the 
State  Board  of  Entomology,"  n.d.,  folder  Ei,  "Rocky  Mountain  Spotted  Fe- 
ver—Research and  Control  (R.  A.  Cooley),  1909-1916,"  box  10,  ZEA. 

54.  Pricks  to  Blue,  15  September  191 3;  and  Howard  to  Blue,  20  August 
1913,  file  1266,  box  119,  Central  File,  1897-1923,  PHS  Records. 


Notes  to  Pages  91-95 


287 


55.  Blue  to  Howard;  and  memorandum  for  the  Secretary,  signed  Rupert 
Blue,  29  September  1913,  file  1266,  box  119,  Central  File,  1897-1923,  PHS 
Records. 

56.  Unsigned  letter  to  Fricks,  1 6  September  1 9 1 3 ,  file  1 266,  box  119,  Central 
File,  1 897-1923,  PHS  Records.  The  writer  appears  to  have  been  Surgeon 
General  Rupert  Blue. 

57.  L.  D.  Fricks,  "Rocky  Mountain  Spotted  Fever:  A  Report  of  Its  Inves- 
tigation and  of  Work  in  Tick  Eradication  for  Its  Control  During  19 13,"  Pub. 
Health  Rep.  29  (i9i4):449-6i  (strength  of  dipping  solutions  is  discussed  on 
p.  452);  Price,  Fighting  Spotted  Fever.,  107. 

58.  Price,  Fighting  Spotted  Fever,  107-9.  the  official  ban  against  com- 
pensation from  state  funds,  see  Butler  to  Cooley,  22  July  1915,  vol.  "Montana 
State  Officials";  also  letters  regarding  compensation  in  vol.  "Numerous  Per- 
sons in  the  Bitterroot  Valley,"  CC. 

59.  Known  as  the  "Laboratory  Dip,"  the  improved  formula  had  been  worked 
out  by  a  South  African  researcher  and  included  arsenite  of  soda,  soft  soap, 
kerosene,  and  water.  See  King,  "Work  of  Bureau  of  Entomology,"  20. 

60.  These  incidents  are  briefly  covered  in  Price,  Fighting  Spotted  Fever.,  1 1 1- 
13.  They  received  scant  mention  in  the  press  and  in  official  archival  corre- 
spondence. See,  for  example,  "Dipping  Vats  Destroyed,"  Northwest  Tribune, 
20  June  19 1 3,  which  reported  that  John  Dunbar  had  been  charged  with 
destroying  the  vat  on  the  James  Dunbar  ranch  northwest  of  Hamilton.  Pros- 
ecution of  Dunbar  is  mentioned  only  briefly  in  D.  M.  Kelly  to  Cooley,  12 
September  191 3,  vol.  "Montana  State  Officials";  and  destruction  of  the  Flor- 
ence vat  is  mentioned  but  not  described  in  Cooley  to  J.  D.  Taylor,  24  June 
191 3,  vol.  "Numerous  Persons  in  the  Bitterroot  Valley,"  CC.  There  is  no 
discussion  of  either  incident  in  the  files  of  the  National  Archives  or  in  any 
official  publications.  Robert  N.  Philip,  however,  in  a  personal  communication 
to  the  author,  16  February  1988,  illuminated  the  incident  of  the  dynamiting 
of  the  Florence  vat.  His  information  was  based  on  an  interview  he  conducted 
on  20  February  1986,  with  Carl  Wemple,  who  had  survived  spotted  fever  after 
a  prolonged  illness.  The  boys'  father,  Philip  stated,  denied  having  had  anything 
to  do  with  the  dynamiting. 

61.  Cooley  to  King,  i  August  191 3,  vol.  "W.  V.  King";  and  C.  H.  Stevens 
to  Cooley,  3  August  19 13,  vol.  "Montana  State  Officials,"  CC;  King,  "Work 
of  Bureau  of  Entomology,"  17-18. 

62.  Fricks,  "Rocky  Mountain  Spotted  Fever:  A  Report,  19 13,"  455;  King, 
"Work  of  the  Bureau  of  Entomology,"  23. 

63.  King,  "Work  of  the  Bureau  of  Entomology,"  19—23;  Fricks,  "Rocky 
Mountain  Spotted  Fever:  A  Report,  191 3,"  451. 

64.  L.  D.  Fricks,  "Rocky  Mountain  Spotted  (or  Tick)  Fever:  Sheep  Grazing 
as  a  Possible  Means  of  Controlling  the  Wood  Tick  (Dermacentor  andersoni) 
in  the  Bitter  Root  Valley,"  Pub.  Health  Rep.  28  (191 3):  1647-53  (quotation 
from  p.  1649);  King  to  Cooley,  6  November  191 5;  and  Cooley  to  King,  19 
November  19 15,  vol.  "W.  V.  King,"  CC. 

65.  Fricks,  "Rocky  Mountain  Spotted  Fever:  A  Report,  1913,"  454. 

66.  Idem,  "Rocky  Mountain  Spotted  (or  Tick)  Fever:  Sheep  Grazing,"  1647— 
49,  1653;  idem,  "Rocky  Mountain  Spotted  Fever:  A  Report,  1913,"  455. 

67.  Idem,  "Rocky  Mountain  Spotted  Fever:  A  Report,  1913,"  456;  idem, 
"Rocky  Mountain  Spotted  (or  Tick)  Fever:  Sheep  Grazing,"  1653. 


288 


Notes  to  Pages  9S-98 


68.  W.  V.  King,  "Report  on  the  Investigation  and  Control  of  the  Rocky 
Mountain  Spotted  Fever  Tick  in  Montana  During  191 5-1 9 16,"  in  MSBE, 
Second  Biennial  Report,  23;  King  to  Cooley,  6  November  191 5,  vol. 
"W.  V.  King,"  CC. 

69.  "Bitter  Root  Sheep  Come  to  the  Rescue,"  Western  News,  14  April  19 14; 
"Sheep  Death  on  Ticks,  Experiments  Prove,"  ibid.,  8  May  19 14. 

70.  Smith  and  Kilbourne,  "Investigations  into  Texas  or  Southern  Cattle 
Fever"  (see  chap.  3,  n.  21). 

71.  Fricks,  "Rocky  Mountain  Spotted  Fever:  A  Report,  19 13,"  452-53. 

72.  Cooley  to  R.  R.  Parker,  24  May  1915,  vol.  "R.  R.  Parker,  1913-1917," 
CC. 

73.  Tabulation  of  spotted  fever  cases  in  Montana  by  county,  191 5,  n.d., 
vol.  "W.  R  Cogswell,  A.  H.  McCray,  T.  D.  Turtle,"  CC;  Robert  A.  Cooley, 
"Control  of  the  Rocky  Mountain  Spotted  Fever  Tick  in  Montana,"  in  MSBE, 
Second  Biennial  Report,  6;  "Report  18  Cases  of  Spotted  Fever,"  Western  News, 
18  May  1915. 

74.  R.  R.  Spencer,  "The  Fleas,  the  Ticks,  Spotted  Fever,  and  Me,"  Saturday 
Review  46  (2  November  i963):48.  Spencer's  background  will  be  discussed  in 
detail  in  chap.  7. 

75.  For  biographical  information  on  Parker  see  Victor  H.  Haas,  "Ralph  R. 
Parker:  1888-1949,"  Science  iii  (i95o):56-57;  American  Men  of  Science, 
5th  ed.  (see  chap.  3,  n.  64),  857;  Who's  Who  in  America:  A  Biographical 
Dictionary  of  Notable  Living  Men  and  Women,  1938-39  (Chicago:  Marquis- 
Who's  Who,  1939),  1935;  "Ralph  R.  Parker,"  in  Jeanette  Barry,  comp..  No- 
table Contributions  to  Medical  Research  by  Public  Health  Service  Scientists: 
A  Bibliography  to  1940  (Washington,  D.C.:  Government  Printing  Office, 
i960),  63-65. 

76.  Cooley  to  Fernald,  10  March  19 14;  and  Fernald  to  Cooley,  17  March 
19 14,  vol.  "Professors  at  Various  Universities,"  CC;  MSBE,  First  Biennial 
Report,  32-34;  R.  R.  Parker  and  R.  W.  Wells,  "Some  Facts  of  Importance 
Concerning  the  Rocky  Mountain  Spotted  Fever  Tick  (Dermacentor  venustus 
Banks)  in  Eastern  Montana,"  in  MSBE,  Second  Biennial  Report,  45-56; 
R.  R.  Parker,  "Second  Report  on  Investigations  of  the  Rocky  Mountain  Spotted 
Fever  Tick  in  Eastern  Montana,"  in  MSBE,  Third  Biennial  Report,  41—54. 
During  his  19 17  work,  Parker  was  assisted  by  young  Harold  C.  Urey,  who 
in  1934  won  a  Nobel  prize  in  chemistry. 

77.  "Regulations  of  the  Montana  State  Board  of  Entomology,"  in  MSBE, 
Second  Biennial  Report,  1 1 ;  Fricks  to  Montana  State  Board  of  Entomology, 
8  November  19 16,  vol.  "Montana  State  Officials";  Cooley  to  King,  16  De- 
cember 1916;  and  King  to  Cooley,  26  and  31  December  1916,  vol.  "W.  V. 
King,"  CC;  Fricks  to  Blue,  4  December  1916,  file  1266,  box  119,  Central  File, 
1897-1923,  PHS  Records. 

78.  Fricks  to  Cooley,  i  February  1917,  folder  2,  "Rocky  Mountain  Spotted 
Fever,  1912— 1919,"  box  i,  "General  Correspondence,"  MSBH  Records. 

79.  Malburn  to  Stewart,  12  December  19 16;  Cogswell  to  Malburn,  27 
December  1916;  and  McAdoo  to  Cogswell,  10  January  1917,  folder  2,  "Rocky 
Mountain  Spotted  Fever,  1912-1919,"  box  i,  "General  Correspondence," 
MSBH  Records. 

80.  Fricks  to  Blue,  9  April  19 17;  Blue  to  Fricks,  24  April  19 17;  Blue  to 
Cogswell,  24  April  1917;  and  "Tick  Quarantine  in  Valley  Lifted  by  State 


Notes  to  Pages  pp-ioz 


289 


Board,"  clipping  from  Daily  Missoulian,  n.d.,  file  1266,  box  119,  Central  File, 
1897— 1923,  PHS  Records;  "Tick  Quarantine  Is  Lifted  along  the  West  Side," 
Western  News,  12  April  19 17. 

81.  Cooley  to  Rankin,  17  July  19 17;  and  Secretary  of  Agriculture  David  F. 
Houston  to  Rankin,  12  September  19 17,  vol.  "Montana  State  Officials,"  CC. 

82.  Cooley  to  S.  Burt  Wolbach,  z6  February  19 18,  vol.  "Professors  at  Various 
Universities,"  CC.  On  Parker's  work  at  Harvard  and  an  illness  he  suffered 
during  this  period,  see  his  correspondence  with  Cooley  from  August  through 
November  1917,  vol.  "R.  R.  Parker,  1913-1917";  and  Parker  to  Cooley,  12 
and  30  March  1918,  vol.  "R.  R.  Parker,  1918-1919,"  CC. 

83.  Parker  to  Cooley,  25  April  1918,  vol.  "R.  R.  Parker,  1918-1919,"  CC; 
"Controlling  the  Tick,"  Western  News,  6  March  1919;  Robert  A.  Cooley, 
"Control  Methods  in  Use,"  in  MSBE,  Third  Biennial  Report,  6;  R.  R.  Parker, 
"Report  of  Tick  Control  Operations  in  the  Bitter  Root  Valley  during  the  Season 
of  19 1 8,  Facts  in  Connection  Therewith;  Recommendations  for  the  Further 
Prosecution  of  the  Work,"  in  MSBE,  Third  Biennial  Report,  25-40;  R.  R. 
Parker,  "Report  of  Tick  Control  Operations  in  the  Bitter  Root  Valley  during 
the  Seasons  of  1919  and  1920,"  in  MSBE,  Fourth  Biennial  Report,  18—44. 

84.  Parker  to  Cooley,  27  January  1919;  and  correspondence  in  April  1919 
between  Parker  and  Cooley  on  stock  owners'  opposition  to  grazing  restrictions, 
vol.  "R.  R.  Parker,  1918-1919,"  CC;  Robert  A.  Cooley,  "Results,"  in  MSBE, 
Third  Biennial  Report,  lo-ii,  17. 

85.  Robert  A.  Cooley,  introductory  remarks  in  MSBE,  Fourth  Biennial 
Report,  5;  idem,  in  Fifth  Biennial  Report,  4;  Price,  Fighting  Spotted  Fever, 
169.  The  Montana  State  Board  of  Entomology  did  not  publish  a  report  to 
cover  the  year  1921. 

86.  Robert  A.  Cooley,  letter  of  transmittal,  in  MSBE,  Fourth  Biennial  Report, 
4.  The  possible  extermination  of  the  mountain  goat  was  first  proposed  in 
Cooley,  "Control  Methods,"  7.  See  also  idem,  "The  Goat  Question,"  press 
release,  18  September  1923,  folder  E4,  "Rocky  Mountain  Spotted  Fever  and 
General  and  Miscellaneous  Health  Services,  1925— 1946,"  box  10,  ZEA;  "The 
Mountain  Goat  or  the  Taxpayers  Goat,"  Northwest  Tribune,  12  October 
1923,  clipping  in  RML  Scrapbook  "1919— 1931." 

87.  Cogswell  to  Surgeon  General  Gumming,  telegram,  22  June  192 1,  cited 
in  Price,  Fighting  Spotted  Fever,  169;  "Spotted  Fever  Causes  2  Deaths,"  West- 
ern News,  9  June  1921;  "Tyler  Worden  of  Missoula  Dies,"  Western  News, 
16  June  1921.  I  am  grateful  to  Robert  N.  Philip  for  information  about  the 
epidemiology  of  the  1921  cases. 

Chapter  Six:  A  Wholly  New  Type  of  Microorganism 

1.  For  a  statement  of  Koch's  postulates,  see  chap.  3,  n.  22;  see  also  Victoria 
A.  Harden,  "Koch's  Postulates  and  the  Etiology  of  Rickettsial  Diseases," 
/.  Hist.  Med.  Allied  Sci.  42  (198 7): 277-9 5. 

2.  E.  R.  LeCount,  "A  Contribution  to  the  Pathological  Anatomy  of  Rocky 
Mountain  Spotted  Fever,"  /.  Inf.  Dis.  8  (i9ii):42i— 26  (quotations  from  pp. 
422,  423,  424). 

3 .  On  Councilman  and  Mallory  see  Esmond  R.  Long,  A  History  of  American 
Pathology  (Springfield,  111.:  Charles  C.  Thomas,  1962),  153—55.  biograph- 
ical information  on  Wolbach  see  Charles  A.  Janeway,  "S.  Burt  Wolbach,  1880- 


290 


Notes  to  Pages  103-s 


1954,"  Trans.  Assn.  Am.  Physicians  67  (i954):30-35;  Shields  Warren,  "Sim- 
eon Burt  Wolbach,  3rd  July  1880— 19th  March  1954,"  Journal  of  Pathology 
and  Bacteriology  68  {i9$4):6$6-^'j;  Sidney  Farber  and  Charlotte  L.  Maddock, 
"S.  Burt  Wolbach,  M.D.,  1 880-1954,"  A.M. A.  Archives  of  Pathology  S9 
(195  5)1624-30;  "S.  Burt  Wolbach,"  in  Esmond  R.  Long,  History  of  the  Amer- 
ican Society  for  Experimental  Pathology  (Bethesda,  Md.:  American  Society 
for  Experimental  Pathology,  1972),  89-90;  "Dr.  S.  B.  Wolbach,  Pathologist, 
Dies,"  New  York  Times,  20  March  1954;  Jeffrey  D.  Hubbard,  "S.  Burt  Wol- 
bach, M.D.,  1 880-1954,"  Pediatric  Pathology  7  (1987): 507-14. 1  am  grateful 
to  Dr.  Hubbard  for  providing  me  with  a  preprint  of  his  paper. 

4.  Wolbach,  "Studies  on  Rocky  Mountain  Spotted  Fever,"  55,  as  cited  in 
chap.  4,  n.  7. 

5.  For  biographical  information  on  Noguchi  see  Isabel  R.  Plesset,  Noguchi 
and  His  Patrons  (Rutherford,  N.J.:  Fairleigh  Dickinson  University  Press,  1980); 
Gustav  Eckstein,  Noguchi  (New  York:  Harper,  193 1);  Paul  Franklin  Clark, 
"Hideyo  Noguchi,  1 876-1928,"  Bull.  Hist.  Med.  33  (1959):  18-19.  My  dis- 
cussion of  Noguchi's  early  spotted  fever  work  follows  Plesset,  Noguchi,  166- 
73- 

6.  Hideyo  Noguchi,  Snake  Venoms:  An  Investigation  of  Venomous  Snakes 
with  Special  Reference  to  the  Phenomena  of  Their  Venoms  (Washington,  D.C.: 
Carnegie  Institution  of  Washington,  1909);  idem,  "A  Method  for  the  Pure 
Cultivation  of  Pathogenic  Treponema  Pallidum  [Spirocheta  pallida),''  Journal 
of  Experimental  Medicine  14  (i9ii):99-io8;  Plesset,  Noguchi,  166;  Noguchi 
to  Fricks,  15  February  19 16,  file  "S.  F.  History  (Correspondence  with  Noguchi, 
1916),"  RML  Research  Records.  Tsutsugamushi  is  discussed  in  more  detail 
later  in  this  chapter. 

7.  L.  D.  Fricks,  "Rocky  Mountain  Spotted  Fever:  A  Report  of  Laboratory 
Investigations  of  the  Virus,"  Pub.  Health  Rep.  31  (i9i6):5i6— 21,  reprinted 
in  MSBE,  Second  Biennial  Report,  28-34  (quotations  from  the  latter,  p.  33). 

8.  Wolbach  to  Cogswell,  21  February  1916,  folder  2,  "Rocky  Mountain 
Spotted  Fever,  19 12-19 19,"  box  i,  "General  Correspondence,"  MSBH  Re- 
cords; Wolbach  to  Cooley,  21  February  and  21  April  19 16;  Cooley  to  Wolbach, 
telegram,  i  March,  and  letter,  8  June  19 16,  vol.  "Professors  at  Various  Uni- 
versities"; and  Cogswell  to  Wolbach,  29  April  1916,  vol.  "W.  F.  Cogswell, 
A.  H.  McCray,  T.  D.  Turtle,"  CC. 

9.  "I  hastened  into  print,"  Wolbach  confided  in  a  letter  to  Fricks,  "because 
of  Noguchi's  competition."  See  Wolbach  to  Fricks,  21  April  1916,  file  "S.  F. 
History  (Correspondence  with  Wolbach  — 1916),"  RML  Research  Records. 

10.  Wolbach  to  Cooley,  14  November  1916,  vol.  "Professors  at  Various 
Universities,"  CC. 

U.S.  Burt  Wolbach,  "The  Etiology  of  Rocky  Mountain  Spotted  Fever  (A 
Preliminary  Report),"  /.  Med.  Res.  34  (i9i6):i2i-25  (quotations  from  pp. 
122-23),  reprinted  in  MSBE,  Second  Biennial  Report,  35-44;  idem,  "The 
Etiology  of  Rocky  Mountain  Spotted  Fever:  Occurrence  of  the  Parasite  in  the 
Tick  (Second  Preliminary  Report),"/.  Med.  Res.  35  (i9i6):i47— 50. 

12.  Plesset,  Noguchi,  170-71;  Noguchi  to  Fricks,  16  October  19 16,  file 
"S.  F.  History  (Correspondence  with  Noguchi  — 19 16),"  RML  Research  Re- 
cords. 

13.  Wolbach  to  Cooley,  13  May  1918,  vol.  "Professors  at  Various  Univer- 
sities," CC. 


Notes  to  Pages  106—8 


14.  McCoy  to  Fricks,  i  May  and  12  June  19 16,  file  "S.  F.  History  (Cor- 
respondence, McCoy  and  Fricks—  General  — 1916),"  RML  Research  Records. 

15.  Wolbach  to  Cooley,  13  December  19 16,  vol.  "Professors  at  Various 
Universities,"  CC. 

16.  S.  Burt  Wolbach,  "The  Etiology  and  Pathology  of  Rocky  Mountain 
Spotted  Fever:  The  Occurrence  of  the  Parasite  and  the  Pathology  of  the  Disease 
in  Man;  Additional  Notes  on  the  Parasite  (Third  Preliminary  Report),"/.  Med. 
Res.  37  (i9i8):499-5o8  (quotation  from  p.  501). 

17.  Ibid.;  Wolbach  to  Chairmen  of  the  State  Boards  of  Entomology  and 
Health,  18  January  19 18,  vol.  "Professors  at  Various  Universities,"  CC  (quo- 
tation from  the  letter). 

18.  Wolbach  to  Cooley,  20  February  191 8,  vol.  "Professors  at  Various 
Universities,"  CC. 

19.  Parker  to  Cooley,  4  June  191 8,  vol.  "R.  R.  Parker,  19 18-19 19"; 
Wolbach  to  Cooley,  2  November  19 18,  vol.  "Professors  at  Various  Univer- 
sities," CC. 

20.  My  discussion  of  Molinscek's  illness  is  based  on  his  hospital  report, 
folder  "Molinscek,"  box  20,  Record  Group  no.  210.3,  Rockefeller  University 
Archives,  New  York;  and  on  Plesset's  discussion  of  the  accident  in  Noguchi, 
173- 

11.  The  records  on  Molinscek's  death  also  provide  an  interesting  view^  of 
legal  and  societal  attitudes  toward  institutional  responsibility  for  the  families 
of  people  who  died  from  laboratory-acquired  infections.  Under  the  New  York 
labor  laws  in  force  at  the  time  of  Molinscek's  death,  the  Rockefeller  Institute 
had  no  legal  responsibility  to  provide  financial  remuneration  to  his  wife  and 
daughter,  both  named  Mary.  As  the  institute's  attorney  advised  its  officials, 
however,  there  was  a  "moral  obligation"  to  do  so,  and  failure  to  provide 
something  might  precipitate  "attacks  from  persons  hostile  to  the  Institute." 
Consequently,  the  board  of  trustees  settled  a  pension  on  Molinscek's  family 
that  was  more  liberal  than  prevailing  Workmen's  Compensation  requirements 
for  deaths  covered  by  the  law.  See  copies  of  the  final  financial  arrangement 
approved  by  members  of  the  Executive  Committee  of  the  Board  of  Scientific 
Directors  of  the  Rockefeller  Institute  dated  29  June  19 18,  folder  "MoHnscek," 
box  20,  Record  Group  no.  210.3,  Rockefeller  University  Archives,  New  York. 

22.  Wolbach,  "Studies  on  Rocky  Mountain  Spotted  Fever,"  83,  87  (see  chap. 
4,  n.  7). 

23.  Ibid.,  84. 

24.  E.  V.  Cowdry,  "The  Distribution  of  Rickettsia  in  the  Tissues  of  Insects 
and  Arachnids,"  /.  Exp.  Med.  37  (i923):43i-56  (quotation  from  pp.  431- 
32).  The  first  major  work  on  the  laboratory  regulation  of  acidity  levels,  or 
pH,  was  William  Mansfield  Clark,  The  Determination  of  Hydrogen  Ions:  An 
Elementary  Treatise  on  the  Hydrogen  Electrode,  Indicators,  and  Supplemen- 
tary Methods,  with  an  Indexed  Bibliography  on  Applications  (Baltimore: 
Williams  &  Wilkins  Co.,  1920). 

25.  Fricks  consistently  denied  that  the  two  organisms  were  the  same.  When 
the  Montana  State  Board  of  Entomology  published  the  two  reports  side  by 
side,  Fricks  complained.  "I  wish  to  disclaim  any  connection  with  the  bacillus 
first  reported  by  Prof.  Wolbach,  and  at  the  same  time  remind  the  Board  that 
the  small,  double  granules  or  protozoan  bodies"  were  "first  described  by  me." 


292 


Notes  to  Pages  lop-iz 


See  Fricks  to  the  Montana  State  Board  of  Entomology,  29  March  19 17,  vol. 
"Montana  State  Officials,"  CC. 

26.  Harry  Plotz,  "The  Etiology  of  Typhus  Fever  (and  of  Brill's  Disease)," 
JAMA  62  (i9i4):i556;  Henrique  da  Rocha  Lima,  "Beobachtungen  bei  Fleck- 
typhuslausen,"  Archiv  fur  Schiffs-  und  Tropen-Hygiene  21  (1916):  17—31; 
Henrique  da  Rocha  Lima,  "Zur  Aetiologie  des  Fleckfiebers,"  Berl.  klin. 
Wchnschr.  53  (19 16)  15  67-72,  Eng.  trans,  in  Nicholas  Hahon,  ed..  Selected 
Papers  on  the  Pathogenic  Rickettsiae  (Cambridge,  Mass.:  Harvard  University 
Press,  1968),  74-78  (quotation  from  pp.  'j6—jy).  Da  Rocha  Lima's  articles 
on  typhus  are  also  reproduced  in  Henrique  da  Rocha  Lima,  Estudos  sobre  o 
Tifo  Exantemdtico,  comp.  Edgard  de  Cerqueira  Falcao,  with  commentary  by 
Otto  G.  Bier  (Sao  Paulo,  Brazil,  1966). 

27.  Wolbach,  "Studies  on  Rocky  Mountain  Spotted  Fever,"  87-88. 

28.  A.  Conor  and  A.  Bruch,  "Une  Fievre  eruptive  observee  en  Tunisie," 
Bulletin  de  la  Societe  de  Pathologie  Exotique  et  de  Ses  Filiales  3  (19 10)  1492- 
96  (hereafter  cited  as  Bull.  Soc.  Path.  Exotique).,  Eng.  trans,  in  Hahon,  ed.. 
Selected  Papers,  47-52  (quotations  from  pp.  47-48). 

29.  Nathan  E.  Brill,  "A  Study  of  17  Cases  of  a  Disease  Clinically  Resembling 
Typhoid  Fever,  but  without  the  Widal  Reaction,"  New  York  Medical  Journal 
67  (i898):48-54,  77-82;  idem,  "An  Acute  Infectious  Disease  of  Unknown 
Origin:  A  Clinical  Study  Based  on  221  Cases,"  Am.  J.  Med.  Sci.  139 
(i9io):484-502. 

30.  Jose  F.  Sant'Anna,  "On  a  Disease  in  Man  Following  Tick  Bites  and 
Occurring  in  Louren^o  Marques,"  Parasitology  4  (i9ii):87— 88. 

31.  George  H.  F.  Nuttall,  "On  Symptoms  Following  Tick-Bites  in  Man," 
Parasitology  4  ( 1 9 1 1 ) :  8  9-9  3 . 

32.  J.  G.  McNaught,  "Paratyphoid  Fevers  in  South  Africa,"  Journal  of  the 
Royal  Army  Medical  Corps  16  (i9ii):505-i4. 

33.  J.  W.  D.  Megaw,  "A  Case  of  Fever  Resembling  Brill's  Disease,"  Indian 
Medical  Gazette  52  (19 17):  15-18  (quotation  from  p.  18.. 

34.  Oliver  Smithson,  "Mossman  Fever,"  Journal  of  Tropical  Medicine  and 
Hygiene  13  (i9io):35i— 52.  A  review  of  reports  from  the  Federated  Malay 
States  is  in  WiUiam  Fletcher,  "Typhus-Like  Fevers  of  Unknown  Etiology,  with 
Special  Reference  to  the  Malay  States,"  Proceedings  of  the  Royal  Society  of 
Medicine  23  (1930):  1021—27  (discussion,  pp.  1027—30). 

3  5 .  My  discussion  follows  Francis  G.  Blake,  Kenneth  F.  Maxcy,  J.  F.  Sadusk, 
G.  M.  Kohls,  and  E.  J.  Bell,  "Studies  on  Tsutsugamushi  Disease  (Scrub  Typhus, 
Mite-Borne  Typhus)  in  New  Guinea  and  Adjacent  Islands:  Epidemiology, 
Clinical  Observations,  and  Etiology  in  the  Dobadura  Area,"  American  Journal 
of  Hygiene  41  (i945):243-72;  J.  R.  Audy,  Red  Mites  and  Typhus  (London: 
Athlone  Press,  1968);  and  Rinya  Kawamura,  "Studies  on  Tsutsugamushi  Dis- 
ease," College  of  Medicine  of  the  University  of  Cincinnati  Medical  Bulletin  4 
(1926),  special  nos.  i,  2. 

36.  Percy  M.  Ashburn  and  Charles  F.  Craig,  "Comparative  Study  of  Tsut- 
sugamushi Disease  and  Spotted  or  Tick  Fever  of  Montana,"  Boston  Medical 
and  Surgical  Journal  159  (1908)  1749-61. 

37.  The  three  initial  papers  describing  trench  fever  were  H.  Topfer,  "Zur 
Aetiologie  des 'Febris  Wolhynica,'  ''Berl.  klin.  Wchnschr.  53  (19 16):  3  23;  idem, 
"Der  Fleckfiebererreger  in  der  Laus,"  Deutsche  Medizinische  Wochenschrift 
42  (19 1 6): 1 25 1— 54  (hereafter  cited  as  Deutsche  med.  Wchnschr.)-,  and  idem. 


Notes  to  Pages  iiz-i^ 


293 


"Zur  Ursache  und  Ubertragung  des  Wolhynischen  Fiebers,"  Muenchener  Med- 
izinische  Wochenschrift  63  (19 16):  1495-96.  For  reviews  of  trench  fever  re- 
search written  shortly  after  World  War  I,  see  David  Bruce,  "Trench  Fever: 
Final  Report  of  the  War  Office  Trench  Fever  Investigation  Committee," /owrw*^/ 
of  Hygiene  20  (i 921):  25  8-8 8;  American  Red  Cross  Medical  Research  Com- 
mittee, Trench  Fever:  Report  of  Commission,  Medical  Research  Committee, 
American  Red  Cross,  by  Richard  R  Strong  (Oxford:  Oxford  University  Press, 
191 8);  H.  R  Swift,  "Trench  Fever,"  Archives  of  Internal  Medicine  26 

(1920)  :76-98. 

38.  "Typhus  Fever  and  Plague  in  Central  Europe," /AMA  99  (i932):i369. 

39.  The  report  of  their  work  is  in  League  of  Red  Cross  Societies,  Typhus 
Research  Commission  to  Poland,  The  Etiology  and  Pathology  of  Typhus^  by 
S.  Burt  Wolbach,  John  L.  Todd,  and  Francis  W  Palfrey  (Cambridge,  Mass.: 
League  of  Red  Cross  Societies,  Harvard  University  Press,  1922)  (hereafter  cited 
as  Wolbach,  Todd,  and  Palfrey,  Etiology  and  Pathology  of  Typhus). 

40.  Parker  to  Cooley,  14  October  1919;  and  Parker  to  Wolbach,  2  December 
1919,  vol.  "R.  R.  Parker,  1918-1919,"  CC.  Parker's  illness  is  referred  to 
variously  as  influenza  and  pneumonia;  it  may  well  have  been  a  combination. 
See  vol.  "R.  R.  Parker,  1920,"  CC. 

41.  Wolbach  to  Cooley,  26  August  1920,  vol.  "Professors  at  Various  Uni- 
versities," CC.  On  Bacot  see  J.  C.  G.  Ledingham,  "In  Memoriam:  Arthur  W 
Bacot,  F.  E.  S.,"  British  Journal  of  Experimental  Pathology  3  (i922):ii7-24. 

42.  Wolbach,  Todd,  and  Palfrey,  Etiology  and  Pathology  of  Typhus.,  3. 

43.  Wolbach,  "Studies  on  Rocky  Mountain  Spotted  Fever,"  183;  Wolbach, 
Todd,  and  Palfrey,  Etiology  and  Pathology  of  Typhus.,  202. 

44.  Wolbach,  Todd,  and  Palfrey,  Etiology  and  Pathology  of  Typhus.,  123— 
24.  One  point  of  disagreement  about  the  definition  of  Rickettsia-bodies  con- 
cerned human  pathogenicity.  Wolbach  maintained  that  only  pathogenic  or- 
ganisms should  be  classified  as  Rickettsia-bodies.  Edmund  V.  Cowdry  of  the 
Rockefeller  Institute,  in  contrast,  argued  that  this  was  not  a  necessary  criterion. 
For  Cowdry's  view  see  E.  V.  Cowdry,  "Rickettsiae  and  Disease,"  Archives  of 
Pathology  and  Laboratory  Medicine  2  (1926): 59— 90. 

45.  Report  of  Berlin  correspondent, /AMA  76  (i92i):i78o;  D.  Montfallet, 
"A  Protozoon  in  Relation  to  Typhus,"  Revista  Medica  de  Chile  48  (i92o):7i8, 
as  abstracted  in  ibid.,  900. 

46.  This  work  was  mentioned  and  rebutted  in  Peter  K.  Olitsky,  "Definition 
of  Experimental  Typhus  in  Guinea-Pigs,"  ibid.  78  (i922):57i-74. 

47.  H.  M.  Woodcock,  "  'Rickettsia'-Bodies  as  a  Result  of  Cell-Digestion  or 
Lysis,"/.  Royal  Army  Med.  Corps  40  (i923):8i-97,  241—69;  idem,  "On  the 
Modes  of  Production  of 'Rickettsia'-Bodies  in  the  Louse,"  ibid.  42  (i924):i2i- 
31,  175—86  (quotation  from  p.  186);  Leo  Loewe,  Saul  Ritter,  and  George 
Baehr,  "Cultivation  of  Rickettsia-Like  Bodies  in  Typhus  Fever,"  JAMA  77 

(1921)  :i967-69. 

48.  Edmund  Weil  and  Arthur  Felix,  "Zur  serologischen  Diagnose  des  Fleck- 
fiebers,"  Wiener  klinische  Wochenschrift  29  (19 16): 3 3-3  5,  Eng.  trans,  in  Ha- 
hon,  ed..  Selected  Papers.,  79-86. 

49.  My  description  follows  Hahon's  comments  in  preface  to  Weil  and  Felix's 
article,  in  Hahon,  ed..  Selected  Papers,  79. 

50.  W.J.  Wilson,  "Serologic  Test  in  Typhus,"  Lancet  i  (i922):222;  Fletcher, 
"Typhus-Like  Fevers,"  1024. 


294 


Notes  to  Pages  iij-iy 


51.  Report  of  Berlin  correspondent, /AMA  76  (i92i):i78o;  B.  Fejgin,  "Au 
sujet  du  serum  de  Kuczynski  et  d'une  variation  du  Proteus  X19  obtenue  a 
partir  de  Rikettsia  provazeki,"  Comptes  Rendus  des  Seances  de  la  Societe  de 
Biologie  et  de  Ses  Filiales  95  (i926):i2o8-io  (hereafter  cited  as  Compt.  rend. 
Soc.  de  bioL);  L.  Anigstein  and  R.  Amzel,  "Recherches  sur  I'etiologie  du  typhus 
exanthematique.  Le  typhus  exanthematique  chez  les  cobazes  infectes  par  les 
cuhures  du  germe,"  Comt.  rend.  Soc.  de  biol.  96  (1927):  1502;  M.  H.  Kuczynski 
and  Ehsabeth  Brandt,  "Neue  atiologische  und  pathogenetische  Untersuchun- 
gen  in  der  'Rickettsiengruppe,'  "  Krankheitsforschung  3  (19 26)  126-74;  Kuc- 
zynski and  Brandt,  Die  Erreger  des  Fleck-  und  Felsenfiebers,  Biologische  und 
Pathogenetische  Studien  (BerHn:  Juhus  Springer,  1927);  abstract  of  M.  Ruiz 
Castaneda  and  S.  Zia,  "Antigenic  Relationship  of  Proteus  X19  to  Typhus 
Rickettsiae,"  in  Arch.  Pathol.  16  (i933):4i9.  Elisabeth  Brandt's  death  was 
noted  in  Richard  Otto,  "Fleckfieber  und  Amerikanisches  Felsengebirgsfieber," 
Centralblatt  fiir  Bakteriologie,  Parasitenkunde,  und  Infektionskrankheiten 
106  (i928):279— 91.  Theodore  E.  Woodward,  who  knew  Felix,  communicated 
to  me  that  Felix  never  gave  up  his  conviction  that  the  etiological  agent  of 
typhus  was  a  variant  of  B.  proteus. 

52.  Frederick  Breinl,  "Betrachtungen,  iiber  die  Immunitat  bei  einigen  Er- 
krankungen  mit  ultravisiblem  Erreger,"  Deutsche  med.  Wchnschr.  51 
(i925):264;  Rudolf  Weigl,  "Der  Gegenwartige  Stand  der  Rickettsiafor- 
schung,"  Klinische  Wochenschrift  3  (i924):i59o— 94,  1636-41;  abstract  of 
I.  W.  Hach,  "Experimental  Typhus.  IV.  Filterability  of  Virus  of  Typhus,"  in 
Arch.  Pathol.  Lab.  Med.  3  (i927):3i8;  abstract  of  P.  Fiauduroy,  "Etiology 
of  Typhus,"  in  "Recent  Research  on  Typhus,"  JAMA  85  (i925):i844;  E.  V. 
Cowdry,  "Rickettsiae  and  Disease,"  Arch.  Pathol.  Lab.  Med.  2  (1926): 59- 
90  (reference  to  Trench  Fever  Commission  on  p.  63). 

53.  S.  B.  Wolbach  and  M.  J.  Schlesinger,  "The  Cultivation  of  the  Microor- 
ganisms of  Rocky  Mountain  Spotted  Fever  {Dermacentroxenus  rickettsi)  and 
of  Typhus  {Rickettsia  prowazeki)  in  Tissue  Plasma  Cultures,"  /.  Med.  Res. 
44  (i923):23i-56;  P.  K.  Olitsky  and  J.  E.  McCartney,  "Experimental  Studies 
on  the  Etiology  of  Typhus  Fever.  V.  Survival  of  the  Virus  in  Collodion  Sacs 
Implanted  Intra-Abdominally  in  Guinea  Pigs,"/.  Exp.  Med.  38  (i928):69i; 
Clara  Nigg  and  Karl  Landsteiner,  "Studies  on  Cultivation  of  Typhus  Fever 
Rickettsia  in  Presence  of  Live  Tissue,"  /.  Exp.  Med.  55  (i932):563-76. 

54.  S.  Burt  Wolbach,  "The  Rickettsiae  and  Their  Relationship  to  Disease," 
JAMA  84  (i925):723— 28  (quotations  from  pp.  723,  728). 

55.  Quoted  in  Hughes,  The  Virus  (see  chap.  3,  n.  23),  86. 

56.  W.  G.  MacCullum,  "A  Survey  of  Our  Present  Knowledge  of  Filterable 
Viruses,"  Arch.  Pathol.  Lab.  Med.  i  (1926)1487-88  (quotations  from  p.  488). 
An  excellent  view  of  the  development  of  virology  is  offered  in  Saul  Benison, 
Tom  Rivers:  Reflections  on  a  Life  in  Medicine  and  Science  (Cambridge:  MIT 
Press,  1967);  on  this  early  period  see  esp.  chaps.  3-6.  Rivers's  views  on  the 
state  of  knowledge  regarding  virus  diseases  were  similar  to  those  of  Mac- 
Cullum; see  excerpts  from  a  paper  on  the  subject  given  by  Rivers  at  a  sym- 
posium sponsored  by  the  Society  of  American  Bacteriologists  in  Benison,  Tom 
Rivers.,  1 10— 1 1 ;  the  entire  text  is  in  T.  M.  Rivers,  "Filterable  Viruses:  A  Critical 
Review,"  Arch.  Pathol.  Lab.  Med.  3  (i927):525-28. 

57.  "Dwarf  Bacteria  and  Pigmy  Protozoa,"  JAMA  94  (i93o):795-96. 

58.  Wendell  M.  Stanley,  "Isolation  of  a  Crystalline  Protein  Possessing  the 
Properties  of  Tobacco-Mosaic  Virus,"  Science  81  (193  5): 644-45;  Lily  E.  Kay, 


Notes  to  Pages  iiy-io 


295 


"W.  M.  Stanley's  Crystallization  of  the  Tobacco  Mosaic  Virus,  1930-1940," 
his  77  (i986):450-72. 

59.  Earlier  definitions  of  "life"  turned  on  the  ability  of  organisms  to  me- 
tabolize and  to  reproduce  themselves  independently.  Viruses  cannot  perform 
these  functions  alone  but  must  take  over  the  genetic  machinery  of  a  functioning 
cell.  Sally  Smith  Hughes  observed,  "With  regard  to  the  nature  of  viruses, 
biochemical  findings  appeared  to  support  the  idea  that  viruses  are  very  large 
molecules,  a  refinement  of  the  nonmicrobial  concept  of  the  virus.  Yet  it  was 
also  true  that  the  ability  of  viruses  to  multiply  and  to  infect  were  properties 
traditionally  associated  with  the  living  state.  Hence  they  possessed  both  an- 
imate and  inanimate  characteristics."  See  Hughes,  The  Virus,  89-92. 

60.  Virus  and  Rickettsial  Diseases,  with  Especial  Consideration  of  Their 
Public  Health  Significance,  Proceedings  of  a  symposium.  Harvard  School  of 
Public  Health,  12-17  June  ^939  (Cambridge,  Mass.:  Harvard  University  Press, 
1940). 

61.  S.  Burt  Wolbach,  "The  Rickettsial  Diseases:  A  General  Survey,"  ibid., 
797-801.  Wolbach  also  noted  that  heartwater  disease  of  sheep,  goats,  and 
cattle  was  the  single  rickettsial  infection  known  to  infect  animals.  Its  etiological 
agent  was  known  as  R.  ruminantium,  and  its  vector  was  the  tick  Amblyomma 
hebraeum. 

6z.  Emile  Brumpt,  Precis  de  Parasitologie  (Paris:  Masson  et  Cie.,  1927), 
883;  Henry  Pinkerton,  "Criteria  for  the  Accurate  Classification  of  the  Rick- 
ettsial Diseases  (Rickettsioses)  and  of  Their  Etiological  Agents,"  Parasitology 
28  (i936):i72-89  (quotation  from  pp.  185-86);  C.  B.  Philip,  "Nomenclature 
of  the  Pathogenic  Rickettsiae,"  Am.  J.  Hyg.  37  (i943):3oi-9;  Philip,  "Family 
Rickettsiaceae  Pinkerton,"  in  Bergey's  Manual  of  Determinative  Bacteriology, 
7th  ed.  (Baltimore:  Williams  &  Wilkins,  1957),  934-57.  On  the  evolution  of 
rickettsial  nomenclature,  see  also  Ida  A.  Bengtson,  "Family  Rickettsiaceae 
Pinkerton,"  in  Bergey's  Manual  of  Determinative  Bacteriology,  6th  ed.  (Bal- 
timore: Williams  &  Wilkins,  1948),  1083-99;  Philip,  "Nomenclature  of  the 
Rickettsiaceae  Pathogenic  to  Vertebrates,"  Ann.  New  York  Acad.  Sci.  56 
(i953):484-94. 

Chapter  Seven:  The  Spencer-Parker  Vaccine 

1.  On  land  prices  see  F.  J.  Clifford  to  Surgeon  General,  26  November  1920; 
and  Surgeon  General  to  Clifford,  7  December  1920,  folder  3,  "Rocky  Moun- 
tain Spotted  Fever,  1920-1926,"  box  i,  "General  Correspondence,"  MSBH 
Records.  On  tourism,  see  Cooley  to  James  C.  Evenden,  3  May  1922,  folder 
E2,  "Tick  Control— General  Correspondence,  1918-1928,"  box  10,  ZEA; 
Cogswell  to  Fricks,  27  March  1922,  file  "S.  F.  History  (Correspondence, 
Spencer  and  Fricks  with  Others— 19 16-192 5),"  RML  Research  Records. 

2.  Charles  H.  Roberts  to  Cogswell,  20  July  1921,  folder  3,  "Rocky  Mountain 
Spotted  Fever,  1920-1926,"  box  i,  "General  Correspondence,"  MSBH  Re- 
cords. 

3.  Report  of  Hygienic  Laboratory,  in  MSBH,  Tenth  Biennial  Report,  5; 
Price,  Fighting  Spotted  Fever  (see  chap.  3,  n.  4),  162. 

4.  Cogswell  to  Surgeon  General  Gumming,  and  Cogswell  to  Henry  L.  Mey- 
ers, telegrams,  22  June  1921,  vol.  "W.  F.  Cogswell,  A.  H.  McCray,  T.  D. 
Tuttle,"  CC;  "U.S.  Launches  New  Fight  on  Spotted  Fever,"  Montana  Record- 
Herald  (Helena),  18  July  1921,  and  "Spotted  Fever  Aid  Is  Urged,"  Montana 


Notes  to  Pages  izo-zj 


Record-Herald,  21  July  192 1;  "Would  Ask  U.S.  to  Help  Fever  Fight,"  Inde- 
pendent (Helena),  22  July  1921,  clippings  in  file  1266,  box  120,  Central  File, 
1897— 1923,  PHS  Records. 

5.  Parran  to  Cumming,  25  July  1921,  folder  3,  "Rocky  Mountain  Spotted 
Fever,  1920-1926,"  box  i,  "General  Correspondence,"  MSBH  Records. 

6.  Cogswell  to  Parran,  26  August  192 1;  and  Eliot  Wadsworth  to  Cogswell, 
telegram,  31  August  1921,  folder  3,  "Rocky  Mountain  Spotted  Fever,  1920- 

1926,  "  box  I,  "General  Correspondence,"  MSBH  Records. 

7.  Fricks  to  Surgeon  General,  24  February  1922,  vol.  "Montana  State  Of- 
ficials," CC. 

8.  J.  W.  Kerr  to  R.  R.  Spencer,  4  March  1922,  folder  E9,  "Bitter  Root  Field 
Station,  Correspondence,  1922— 1927,"  box  10,  ZEA.  For  biographical  in- 
formation on  Spencer  see  Spencer,  "The  Fleas,  the  Ticks,  Spotted  Fever,  and 
Me"  cited  in  chap.  5,  n.  74  (quotation  from  p.  47);  R.  R.  Spencer  oral  history 
interview  by  Harlan  Phillips,  in  George  Rosen,  "Transcripts  of  Oral  History 
Project,  1962— 1964,"  NLM  (hereafter  cited  as  Spencer  oral  history);  Michael 
B.  Shimkin,  "Historical  Note:  Roscoe  Roy  Spencer  (i 888-1982)," /owrw^z/  of 
the  National  Cancer  Institute  72  (i984):969-7i;  "Roscoe  R.  Spencer,"  in 
Barry,  Notable  Contributions  (see  chap.  5,  n.  75),  79-81;  "Roscoe  R.  Spencer," 
Pittsburgh  Medical  Bulletin  39  (194 8)1397;  Williams,  United  States  Public 
Health  Service  (see  chap.  3,  n.  39),  195—99. 

9.  Fricks  to  Cogswell,  22  March  1922;  and  Cogswell  to  Fricks,  27  March 
1922,  file  "S.  F.  History  (Correspondence,  Spencer  and  Fricks  with  Others  — 
1916— 1925),"  RML  Research  Records. 

10.  Spencer  to  J.  W.  Schereschewsky,  16  March  1922;  and  Parker  to  Cooley, 
23  May  1923,  folder  E9,  "Bitter  Root  Field  Station,  Correspondence,  1922- 

1927,  "  box  10,  ZEA. 

11.  Fricks  to  J.  W.  Schereschewsky,  23  November  1923,  file  "S.  F.  History 
(Correspondence,  Spencer  and  Fricks  with  Others— 1916-1925),"  RML  Re- 
search Records.  There  was  much  correspondence  about  this  issue  during  1923 
between  Parker  and  Cooley.  See  folder  E9,  "Bitter  Root  Field  Station,  Cor- 
respondence, 1922-1927,"  box  10,  ZEA. 

12.  Spencer  to  Surgeon  General,  10  April  and  5  June  1922,  file  1266,  box 
119,  Central  File,  1897— 1923,  PHS  Records. 

13.  Spencer  to  Surgeon  General,  5  June  1922,  file  1266,  box  119,  Central 
File,  1 897-1923,  PHS  Records.  This  work  was  published  as  R.  R.  Spencer 
and  R.  R.  Parker,  "Rocky  Mountain  Spotted  Fever:  Infectivity  of  Fasting  and 
Recently  Fed  Ticks,"  Pub.  Health  Rep.  38  (1923): 3 3 3-39.  It  was  reprinted 
as  a  part  of  a  collection  of  Spencer  and  Parker's  spotted  fever  papers  in  "Studies 
on  Rocky  Mountain  Spotted  Fever,"  U.S.  Hygienic  Laboratory  Bulletin  no. 
154  (1930),  1-7. 

14.  Spencer  to  Surgeon  General,  5  June  1922;  and  10  April  1922,  file  1266, 
box  119,  Central  File,  1 897-1923,  PHS  Records. 

15.  Spencer  to  Fricks,  15  June  1922,  file  "S.  F.  History  (Correspondence, 
Spencer  and  Fricks  with  Others  — 19 16-192 5),"  RML  Research  Records. 

16.  "A  Hero  of  the  Bitter  Root  Valley";  and  "Research  Worker  Dies  of 
Virulence  He  Is  Combatting,"  Daily  Missoulian,  i  July  1922,  clippings  in 
folder  E3,  "Rocky  Mountain  Spotted  Fever  Fatalities,  1922-1928,"  box  10, 
ZEA;  Price,  Fighting  Spotted  Fever  (see  chap.  3,  n.  4),  179-81. 


Notes  to  Pages  12^-28 


297 


17.  Spencer  to  Surgeon  General,  13  April  1923;  and  Spencer  to  A.  M. 
Stimson,  14  May  1923,  file  1266,  box  119,  Central  File,  1 897-1923,  PHS 
Records;  R.  R.  Spencer,  "Experimental  Studies  on  the  Virus  of  Rocky  Moun- 
tain Spotted  Fever,"  in  "Rocky  Mountain  Spotted  Fever,"  Montana  State  Board 
of  Health  Special  Bulletin  no.  26  (i923):40-44;  R.  R.  Spencer  and  R.  R. 
Parker,  "Rocky  Mountain  Spotted  Fever:  Viability  of  the  Virus  in  Animal 
Tissues,"  Pub.  Health  Rep.  39  (i924):55-57. 

18.  Spencer  to  Surgeon  General,  13  April  1923;  untitled  memo,  apparently 
to  the  surgeon  general  from  G.  W.  McCoy,  7  May  1923;  and  Gumming  to 
Spencer,  10  May  1923,  file  1266,  box  119,  Central  File,  1897— 1923,  PHS 
Records. 

19.  Hideyo  Noguchi,  "Immunity  Studies  of  Rocky  Mountain  Spotted  Fever. 

I.  Usefulness  of  Immune  Serum  in  Suppressing  an  Impending  Infection," 
/.  Exp.  Med.  37  (19 23):3 83-94  (quotations  from  pp.  383,  394). 

20.  Parker  to  Cooley,  18  November  1922,  vol.  "R.  R.  Parker,  1921-1925," 
CC;  Noguchi  to  Cogswell,  30  December  1922,  folder  3,  "Rocky  Mountain 
Spotted  Fever,  19 20-1 9 26,"  box  i,  "General  Correspondence,"  MSBH 
Records. 

21.  Hideyo  Noguchi,  "Immunity  Studies  of  Rocky  Mountain  Spotted  Fever. 

II.  Prophylactic  Inoculation  in  Animals,"  /.  Exp.  Med.  38  (1923)  1605-26 
(quotation  from  p.  625);  idem,  "Prophylactic  Inoculation  against  Rocky 
Mountain  Spotted  Fever,"  in  "Rocky  Mountain  Spotted  Fever,"  Montana  State 
Board  of  Health  Special  Bulletin  no.  26  (i923):44— 47. 

22.  Forew^ord,  in  "Rocky  Mountain  Spotted  Fever,"  Montana  State  Board 
of  Health  Special  Bulletin  no.  26  (i923):3. 

23.  "Dr.  H.  Noguchi  Is  Enthusiastic  Man,"  6  April  1923,  clipping  marked 
"either  Daily  Missoulian  or  Missoula  Sentinel''-,  and  "Spotted  Fever  Heroes: 
Noguchi's  Countrymen  Submit  to  His  Serum,"  Missoula  Sentinel,  12  April 
1923,  clippings  in  RML  Scrapbook  "1919— 1931";  "A  Death  Gamble:  Martyrs 
to  Risk  Lives  to  Aid  Science,"  press  release  in  folder  3,  "Rocky  Mountain 
Spotted  Fever,  1920— 1926,"  box  i,  "General  Correspondence,"  MSBH  Re- 
cords. 

24.  Spencer  oral  history,  59—62;  "Annual  Report  on  Rocky  Mountain  Spot- 
ted Fever  Investigations,"  [1923],  file  1266,  box  119,  Central  File,  1897-1923, 
PHS  Records. 

25.  Parker  to  Cooley,  12  July  1923,  vol.  "R.  R.  Parker,  1921-1925,"  CC. 

26.  Michky  lived  in  the  schoolhouse  laboratory  in  order  to  be  available 
twenty-four  hours  a  day.  See  job  description  on  untitled  personnel  list,  192 1, 
file  1266,  box  119,  Central  File,  1897-1923,  PHS  Records. 

27.  Cogswell  to  Noguchi,  7  September  1923;  Spencer  to  Noguchi,  20  Sep- 
tember 1923;  and  Noguchi  to  Spencer,  27  September  1923,  folder  3,  "Rocky 
Mountain  Spotted  Fever,  1920-1926,"  box  i,  "General  Correspondence," 
MSBH  Records;  Spencer  to  Surgeon  General,  15  August  1923;  and  "Spotted 
Fever  Vaccine  Fails  to  Protect  Boy,"  Anaconda  Standard,  13  August  1923, 
clipping  in  file  1266,  box  119,  Central  File,  1897-1923,  PHS  Records. 

28.  Parker  to  Cooley,  28  February  1925,  vol.  "R.  R.  Parker,  1921-1925," 
CC.  For  Noguchi's  later  work  on  spotted  fever,  see  Hideyo  Noguchi,  "Cul- 
tivation of  Rickettsia-Like  Microorganisms  from  the  Rocky  Mountain  Spotted 
FeverTick,  Dermacentor  andersoni,""  J.  Exp.  Med.  43  (i926):5i5-32;  Hideyo 


298 


Notes  to  Pages  128-^0 


Noguchi,  "A  Filter-Passing  Virus  Obtained  from  Dermacentor  andersoni^'"  ]. 
Exp.  Med.  44  (1926): i-io.  On  the  yellow  fever  research  that  led  to  Noguchi's 
death,  see  Plesset,  Noguchi  (see  chap.  6,  n.  5),  chaps.  21-22;  and  Claude  E. 
Dolman,  "Hideyo  Noguchi  (1876-1928):  His  Final  Effort,"  Clio  Medica  12 
(i977):i3i-45. 

29.  R.  R.  Spencer  and  R.  R.  Parker,  "Rocky  Mountain  Spotted  Fever: 
Experimental  Studies  on  Tick  Virus,"  Pub.  Health  Rep.  39  (i924):3027-4o; 
idem,  "Rocky  Mountain  Spotted  Fever:  Nonfiltrability  of  Tick  and  Blood 
Virus,"  ibid.,  3251-55;  R.  R.  Parker  and  R.  R.  Spencer,  "A  Study  of  the 
Relationship  between  the  Presence  of  Rickettsialike  Organisms  in  Tick  Smears 
and  the  Infectiveness  of  the  Same  Ticks,"  ibid.,  41  (i926):46i-69;  idem, 
"Certain  Characteristics  of  Blood  Virus,"  ibid.,  1817-22. 

30.  Frederick  Breinl,  "Studies  on  Typhus  Virus  in  the  Louse,"  /.  Inf.  Dis. 
34  (1924):  1-12,  abstracted  in  JAMA  82  {19 14): 49^—98.  Spencer's  accounts 
of  his  work  in  developing  the  vaccine  are  in  Spencer  to  Esther  Gaskins  Price 
Ingraham,  10  October  1945,  folder  E5,  "Rocky  Mountain  Spotted  Fever 
History— Correspondence,  1942-1947,"  box  10,  ZEA;  Spencer  oral  history, 
85—87;  Spencer,  "The  Fleas,  the  Ticks,  Spotted  Fever,  and  Me." 

31.  Spencer  and  Parker,  "Rocky  Mountain  Spotted  Fever:  Experimental 
Studies  on  Tick  Virus,"  21—22.  There  was  some  debate  at  first  about  whether 
the  phenol  killed  or  attenuated  the  organisms,  for  prevailing  opinion  argued 
that  only  attenuated  organisms  conferred  immunity.  Guinea  pig  studies  con- 
vinced Spencer  that  the  organism  was  indeed  killed,  and  he  observed,  "We 
are  inclined  to  believe  that  the  killed  as  well  as  the  live  virus  of  Rocky  Mountain 
spotted  fever  can  immunize."  See  R.  R.  Spencer  and  R.  R.  Parker,  "Improved 
Method  of  Manufacture  of  the  Vaccine  and  a  Study  of  Its  Properties,"  in  idem, 
"Studies  on  Rocky  Mountain  Spotted  Fever,"  68-69. 

32.  Price,  Fighting  Spotted  Fever.,  195—96.  Earl  W.  Malone,  who  became 
chief  vaccine  maker,  also  wanted  to  take  the  experimental  vaccine,  but  Spencer 
cautioned  him  to  wait  until  it  was  clear  how  the  vaccine  affected  one  person. 
See  Spencer  to  W.  L.  Jellison,  9  May  1966,  NIAID  files,  NIH  Historical  Office. 

33.  G.  W.  McCoy,  "A  Plague-Like  Disease  in  Rodents,"  Public  Health 
Bulletin  no.  43  (19 11): 5 3-71;  G.  W.  McCoy  and  C.  W.  Chapin,"Further 
Observations  on  a  Plague-Like  Disease  of  Rodents  with  a  Preliminary  Note 
on  the  Causative  Agent,  Bacterium  tularense,''  J.  Inf.  Dis.  10  (19 12): 6 1-72; 
G.  W.  McCoy  and  C.  W.  Chapin,  ''Bacterium  tularense,  the  Cause  of  a  Plague- 
Like  Disease  of  Rodents,"  Public  Health  Bulletin  no.  5  3  ( 1 9 1 2) :  1 7-23 ;  Edward 
Francis,  "Deer-Fly  Fever,  or  Pahvant  Valley  Plague:  A  Disease  of  Man  of 
Hitherto  Unknown  Etiology,"  Pub.  Health  Rep.  34  (i9i9):2o6i-62;  "Tu- 
laremia Francis  1921:  A  New  Disease  of  Man,"  U.S.  Hygienic  Laboratory 
Bulletin  no.  130  (1922),  87  pp.;  Edward  Francis,  "Tularemia,"  JAMA  84 
(i925):i243-5o;  Parker  to  Cooley,  24  August  1924,  vol.  "R.  R.  Parker,  1921- 
1925,"  CC;  Price,  Fighting  Spotted  Fever,  194-97. 

34.  Untitled  personnel  list,  1921,  file  1266,  box  119.  Central  File,  1897- 
1923,  PHS  Records;  "Tick  Worker  Succumbs;  Spotted  Fever  Is  Fatal,"  Daily 
Missoulian,  30  October  1924,  clipping  in  notebook  "RMSF  Laboratory  In- 
fections—Book I,"  R.  R.  Parker  Notebooks,  RML  Research  Records. 

35.  "Tick  Worker  Succumbs,"  Daily  Missoulian,  30  October  1924;  Spencer, 
"The  Fleas,  the  Ticks,  Spotted  Fever,  and  Me,"  49. 


Notes  to  Pages  130-^6 


299 


36.  Noguchi,  cited  in  Spencer  to  Surgeon  General,  28  March  192.5,  file 
0425-32,  "Spotted  Fever— Hamilton,  Montana,"  box  158,  "Domestic  Sta- 
tions, Hamilton,  Montana,"  PHS  Records;  R.  R.  Spencer  and  R.  R.  Parker, 
"Rocky  Mountain  Spotted  Fever:  Vaccination  of  Monkeys  and  Man,"  Pub. 
Health  Rep.  40  (i925):2i59-67;  reprinted  in  idem,  "Studies  on  Rocky  Moun- 
tain Spotted  Fever,"  28-36. 

37.  Cooley  to  Parker,  24  May  1926,  vol.  "R.  R.  Parker,  1926-193 1,"  CC; 
R.  R.  Spencer  and  R.  R.  Parker,  "Rocky  Mountain  Spotted  Fever:  Vaccination 
of  Monkeys  and  Man,"  in  idem,  "Studies  on  Rocky  Mountain  Spotted  Fever," 
31-32. 

38.  Spencer  and  Parker,  "Rocky  Mountain  Spotted  Fever:  Vaccination  of 
Monkeys  and  Man,"  34-35. 

39.  Spencer  to  Surgeon  General,  28  March  1925,  file  0425-32,  "Spotted 
Fever  — Hamilton,  Montana,"  box  158,  "Domestic  Stations,  Hamilton,  Mon- 
tana," PHS  Records;  Parker's  cover  letter  to  Surgeon  General,  9  April  1926 
in  RML,  Monthly  Report,  March  1926.  On  Spencer's  illness  see  Parker  to 
Cooley,  16  March  1926,  vol.  "R.  R.  Parker,  1926-193 1,"  CC. 

40.  R.  R.  Spencer  and  R.  R.  Parker,  "Results  of  Four  Years'  Human  Vac- 
cination," in  idem,  "Studies  on  Rocky  Mountain  Spotted  Fever,"  72-103,  esp. 
89—95;  [Parker]  to  Cooley,  7  July  1926,  folder  3,  "Rocky  Mountain  Spotted 
Fever,  1920-1926,"  box  i,  "General  Correspondence,"  MSBH  Records. 

41.  Spencer  and  Parker,  "Results  of  Four  Years'  Human  Vaccination,"  75— 
78;  Parker  to  Surgeon  General,  telegram,  18  August  1926,  file  0425-183, 
"Spotted  Fever,  Hamilton,  Montana,"  box  158,  "Domestic  Stations  — Ham- 
ilton, Montana,"  PHS  Records;  Parker  to  Surgeon  General,  31  August  1926, 
folder  3,  "Rocky  Mountain  Spotted  Fever,  1920— 1926,"  box  i,  "General  Cor- 
respondence," MSBH  Records;  Parker  to  Surgeon  General,  30  September 
1926,  RML  Monthly  Report,  August  and  September  1926  (quotations  from 
this  report). 

42.  Spencer  and  Parker,  "Results  of  Four  Years'  Human  Vaccination,"  81- 
89. 

43.  R.  R.  Parker,  "Rocky  Mountain  Spotted  Fever:  Results  of  Ten  Years' 
Prophylactic  Vaccination," /.  Inf.  Dis.  57  (i935):78— 93;  idem,  "Rocky  Moun- 
tain Spotted  Fever:  Results  of  Fifteen  Years'  Prophylactic  Vaccination,"  Amer- 
ican Journal  of  Tropical  Medicine  21  (i94i):369-83. 

44.  The  various  methods  tried  are  documented  in  RML,  Monthly  Reports; 
RML,  Annual  Reports;  Earl  W.  Malone,  "Methods  of  Rearing  Dermacentor 
andersoni  for  the  Manufacture  of  Rocky  Mountain  Spotted  Fever  Vaccine"; 
Earl  W.  Malone,  "Preparation  of  Rocky  Mountain  Spotted  Fever  Tick-Tissue 
Vaccine,"  unpublished  technical  reports,  RML;  R.  R.  Spencer  and  R.  R.  Parker, 
"Improved  Method  of  Manufacture  of  the  Vaccine  and  a  Study  of  Its  Prop- 
erties," m  idem,  "Studies  on  Rocky  Mountain  Spotted  Fever,"  63-72.  My 
description  of  the  vaccine-making  process  is  based  on  these  documents  and 
on  Price,  Fighting  Spotted  Fever,  213-21. 

45.  As  the  quantity  of  vaccine  increased  over  the  years,  it  became  necessary 
to  arrange  for  on-site  sterility  testing.  In  1934  technician  Max  T.  McKee 
w^as  sent  to  Bethesda  to  learn  the  techniques,  and  funds  w^ere  allocated  for  a 
special  room  with  incubators  necessary  for  the  process  at  the  Spotted  Fever 
Laboratory  in  Montana.  See  RML,  Monthly  Report,  November  1934,  3;  RML, 
Annual  Report.,  ^93  5?  3-4- 


300 


Notes  to  Pages  1^6-40 


46.  This  article  was  reprinted  as  one  chapter  in  Paul  de  Kruif,  Men  against 
Death  (New  York:  Harcourt,  Brace  &  Co.,  1932),  119-45. 

47.  The  quotations  were  noted  as  objectionable  passages  in  "An  Outside 
View  of  Bitter  Root  Valley,"  Ravalli  Republican,  31  March  1927,  clipping  in 
RML  Scrapbook  "1919-1931." 

48.  Ibid.;  "Bitter  Root  Valley  Is  Up  in  Arms,"  Northwest  Tribune,  3  March 
1927,  clipping  in  RML  Scrapbook  "1919-1931";  Knight  to  Leavitt,  28  Feb- 
ruary 1929,  file  0243-183,  "Hamilton,  Montana,  Chamber  of  Commerce," 
box  44,  "Montana  Cities  and  Counties,"  State  Boards  of  Health,  1924-193  5; 
and  Cumming  to  Parker,  9  March  1929,  file  0425-183,  "Hamilton,  Montana," 
box  158.  "Domestic  Stations,  Hamilton,  Montana,"  PHS  Records. 

49.  Cogswell  to  Pearl  I.  Smith,  n.d.;  and  F.  J.  O'Donnell  to  Cogswell